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Literature review of patients with KCNQ2 developmental and epileptic encephalopathy (KCNQ2‐DEE) reveals, based on 16 reports including 139 patients, a clinical phenotype that includes age‐ and disease‐specific stereotyped seizures. The typical seizure type of KCNQ2‐DEE, focal tonic, starts within 0‐5 days of life and is readily captured by video‐electroencephalography VEEG for clinical and genetic diagnosis. After initial identification, KCNQ2‐DEE seizures are clinically apparent and can be clearly identified without the use of EEG or VEEG. Therefore, we propose that the 2019 recommendations from the International League against Epilepsy (ILAE), the Pediatric Epilepsy Research Consortium (PERC), for capturing and recording seizures for clinical trials (Epilepsia Open, 4, 2019, 537) are suitable for use in KCNQ2‐DEE‒associated antiseizure medicine (ASM) treatment trials. The ILAE/PERC consensus guidance states that a caregiver‐maintained seizure diary, completed by caregivers who are trained to recognize seizures using within‐patient historical recordings, accurately captures seizures prospectively in a clinical trial. An alternative approach historically endorsed by the Food and Drug Administration (FDA) compares seizure counts captured on VEEG before and after treatment. A major advantage of the ILAE/PERC strategy is that it expands the numbers of eligible patients who meet inclusion criteria of clinical trials while maintaining accurate seizure counts (Epilepsia Open, 4, 2019, 537). Three recent phase 3 pivotal pediatric trials investigating ASMs to treat syndromic seizures in patients as young as 2 years of age (N Engl J Med, 17, 2017, 699; Lancet, 21, 2020, 2243; Lancet, 17, 2018, 1085); and ongoing phase 2 open‐label pediatric clinical trial that includes pediatric epileptic syndromes as young as 1 month of age (Am J Med Genet A, 176, 2018, 773), have already used caregiver‐maintained seizure diaries successfully. For determining the outcome of a KCNQ2‐DEE ASM treatment trial, the use of a seizure diary to count seizures by trained observers is feasible because the seizures of KCNQ2‐DEE are clinically apparent. This strategy is supported by successful precedent in clinical trials in similar age groups and has the endorsement of the international pediatric epilepsy community.

Congenital disorders of glycosylation (CDG) are metabolic disorders that affect the glycosylation of proteins and lipids. Since glycosylation affects all organs, CDG show a wide spectrum of phenotypes. We present a patient with microcephaly, dysmorphic facies, congenital heart defect, focal epilepsy, infantile spasms, skeletal dysplasia, and a type 1 serum transferrin isoelectrofocusing due to a novel CDG caused by a homozygous variant in the oligosaccharyltransferase complex noncatalytic subunit (OSTC) gene involved in glycosylation and confirmed by serum transferrin electrophoresis.

The ketogenic diet (KD) is an effective treatment option for intractable epilepsy. Here, we reviewed the last 10 years of our experience with the KD and characterized its use in patients under 3 years of age. Medical records of all patients under the age of 3 years who were treated with the ketogenic diet from April 2004 to June 2014 were retrospectively reviewed. One hundred and nine patients with drug-resistant epilepsy were included. The mean age at the initiation of the KD was 1.4 ± 0.8 years old. The youngest patient was 3 weeks old. After 3 months, 39% (42/109) of patients responded to the KD and experienced more than 50% seizure reduction. Of those 42 patients, 20 (18%) achieved complete seizure control. Patients with a genetic etiology showed a better response to the KD in seizure reduction than the other patients (p = 0.03). Age at initiation of the KD was not related to eventual seizure outcome (p = 0.6). The KD continues to be an effective, safe, and well tolerated treatment option for infants with intractable epilepsy.

There are no evidence-based guidelines on the preferred approach to treating early-life epilepsy. We examined initial therapy selection in a contemporary US cohort of children with newly diagnosed, nonsyndromic, early-life epilepsy (onset before age three years).Seventeen pediatric epilepsy centers participated in a prospective cohort study of children with newly diagnosed epilepsy with onset under 36 months of age. Details regarding demographics, seizure types, and initial medication selections were obtained from medical records.About half of the 495 enrolled children with new-onset, nonsyndromic epilepsy were less than 12 months old at the time of diagnosis (n = 263, 53%) and about half (n = 260, 52%) had epilepsy with focal features. Of 464 who were treated with monotherapy, 95% received one of five drugs: levetiracetam (n = 291, 63%), oxcarbazepine (n = 67, 14%), phenobarbital (n = 57, 12%), topiramate (n = 16, 3.4%), and zonisamide (n = 13, 2.8%). Phenobarbital was prescribed first for 50 of 163 (31%) infants less than six months old versus seven of 300 (2.3%) of children six months or older (P 0.0001). Although the first treatment varied across study centers (P 0.0001), levetiracetam was the most commonly prescribed medication regardless of epilepsy presentation (focal, generalized, mixed/uncertain). Between the first and second treatment choices, 367 (74%) of children received levetiracetam within the first year after diagnosis.Without any specific effort, the pediatric epilepsy community has developed an unexpectedly consistent approach to initial treatment selection for early-life epilepsy. This suggests that a standard practice is emerging and could be utilized as a widely acceptable basis of comparison in future drug studies.

Neurologic care in lower- and middle-income countries is an increasing focus for the field and training of its next generation. The International Issues article features a guide for trainees seeking information on predeparture, funding, and postdeparture advice for global health rotations. The Clinical Reasoning and Teaching Image articles review the workup and management of reversible cerebral vasoconstriction syndrome, ataxia, and new-onset clonus in the setting of fever and confusion.

RATIONALE: Early-life epilepsies (ELEs) include some of the most challenging forms of epilepsy to manage. Given recent diagnostic and therapeutic advances, a contemporary assessment of the immediate short-term outcomes can provide a valuable framework for identifying priorities and benchmarks for evaluating quality improvement efforts. METHODS: Children with newly diagnosed epilepsy and onset

Advances in genetic testing have led to the identification of increasing numbers of novel gene mutations that underlie infantile-onset epileptic encephalopathies. Recently, a mutagenesis screen identified a novel gene, SZT2, with no known protein function that has been linked to epileptogenesis in mice. Thus far, two clinical reports have identified children with different recessive mutations in SZT2 and varying clinical phenotypes. One case report described patients with epileptic encephalopathy and the other noted patients with cognitive deficiencies, but normal MRI and no epilepsy. This case report identifies novel mutations (a compound heterozygous frameshift and a nonsense variant) in the SZT2 gene with distinct clinical and radiographic findings relative to those previously reported. Our patient presented with intractable epilepsy at 2 months of age. Seizures were refractory to numerous antiepileptic medications and the patient finally achieved seizure cessation at age 3 years with a combination of divalproex and lamotrigine. Our patient had similar facial dysmorphisms (macrocephaly, high forehead, and down-slanted palpebral fissures) to a previous case with truncating mutation. While developmental delay and cognitive deficiencies were present, our case had unique MRI findings suggesting migrational abnormalities not previously reported in other cases.

Objective Infantile spasms are seizures associated with a severe epileptic encephalopathy presenting in the first 2 years of life, and optimal treatment continues to be debated. This study evaluates early and sustained response to initial treatments and addresses both clinical remission and electrographic resolution of hypsarrhythmia. Secondarily, it assesses whether response to treatment differs by etiology or developmental status. Methods The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of infantile spasms. Children were considered responders if there was clinical remission and resolution of hypsarrhythmia that was sustained at 3 months after first treatment initiation. Standard treatments of adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin were considered individually, and all other nonstandard therapies were analyzed collectively. Developmental status and etiology were assessed. We compared response rates by treatment group using chi-square tests and multivariate logistic regression models. Results Two hundred thirty infants were enrolled from 22 centers. Overall, 46% of children receiving standard therapy responded, compared to only 9% who responded to nonstandard therapy (p Interpretation Response rate varies by treatment choice. Standard therapies should be considered as initial treatment for infantile spasms, including those with impaired development or known structural or genetic/metabolic etiology. ACTH appeared to be more effective than other standard therapies.

Author(s): Lacuey, Nuria; Zonjy, Bilal; Hampson, Johnson P; Rani, MR Sandhya; Zaremba, Anita; Sainju, Rup K; Gehlbach, Brian K; Schuele, Stephan; Friedman, Daniel; Devinsky, Orrin; Nei, Maromi; Harper, Ronald M; Allen, Luke; Diehl, Beate; Millichap, John J; Bateman, Lisa; Granner, Mark A; Dragon, Deidre N; Richerson, George B; Lhatoo, Samden D | Abstract: OBJECTIVE:The aim of this study was to investigate periictal central apnea as a seizure semiological feature, its localizing value, and possible relationship with sudden unexpected death in epilepsy (SUDEP) pathomechanisms. METHODS:We prospectively studied polygraphic physiological responses, including inductance plethysmography, peripheral capillary oxygen saturation (SpO2 ), electrocardiography, and video electroencephalography (VEEG) in 473 patients in a multicenter study of SUDEP. Seizures were classified according to the International League Against Epilepsy (ILAE) 2017 seizure classification based on the most prominent clinical signs during VEEG. The putative epileptogenic zone was defined based on clinical history, seizure semiology, neuroimaging, and EEG. RESULTS:Complete datasets were available in 126 patients in 312 seizures. Ictal central apnea (ICA) occurred exclusively in focal epilepsy (51/109 patients [47%] and 103/312 seizures [36.5%]) (P l .001). ICA was the only clinical manifestation in 16/103 (16.5%) seizures, and preceded EEG seizure onset by 8 ± 4.9 s, in 56/103 (54.3%) seizures. ICA ≥60 s was associated with severe hypoxemia (SpO2 l75%). Focal onset impaired awareness (FOIA) motor onset with automatisms and FOA nonmotor onset semiologies were associated with ICA presence (P l .001), ICA duration (P = .002), and moderate/severe hypoxemia (P = .04). Temporal lobe epilepsy was highly associated with ICA in comparison to extratemporal epilepsy (P = .001) and frontal lobe epilepsy (P = .001). Isolated postictal central apnea was not seen; in 3/103 seizures (3%), ICA persisted into the postictal period. SIGNIFICANCE:ICA is a frequent, self-limiting semiological feature of focal epilepsy, often starting before surface EEG onset, and may be the only clinical manifestation of focal seizures. However, prolonged ICA (≥60 s) is associated with severe hypoxemia and may be a potential SUDEP biomarker. ICA is more frequently seen in temporal than extratemporal seizures, and in typical temporal seizure semiologies. ICA rarely persists after seizure end. ICA agnosia is typical, and thus it may remain unrecognized without polygraphic measurements that include breathing parameters.

Comparative Effectiveness of Levetiracetam vs Phenobarbital for Infantile Epilepsy Grinspan ZM, Shellhaas RA, Coryell J, Sullivan JE, Wirrell EC, Mytinger JR, Gaillard WD, Kossoff EH, Valencia I, Knupp KG, Wusthoff C, Keator C, Ryan N, Loddenkemper T, Chu CJ, Novotny EJ Jr, Millichap J, Berg AT. JAMA Pediatr. 2018 Apr 1;172(4):352-360. doi: 10.1001/jamapediatrics.2017.5211.More than half of infants with new-onset epilepsy have electroencephalographic and clinical features that do not conform to known electroclinical syndromes (ie, nonsyndromic epilepsy). Levetiracetam and phenobarbital are the most commonly prescribed medications for epilepsy in infants, but their comparative effectiveness is unknown.To compare the effectiveness of levetiracetam versus phenobarbital for nonsyndromic infantile epilepsy.The Early Life Epilepsy Study-a prospective, multicenter, observational cohort study conducted from March 1, 2012, to April 30, 2015, in 17 US medical centers-enrolled infants with nonsyndromic epilepsy and a first afebrile seizure between 1 month and 1 year of age. Exposures: Use of levetiracetam or phenobarbital as initial monotherapy within 1 year of the first seizure. Main Outcomes and Measures: The binary outcome was freedom from monotherapy failure at 6 months, defined as no second prescribed antiepileptic medication and freedom from seizures beginning within 3 months of initiation of treatment. Outcomes were adjusted for demographics, epilepsy characteristics, and neurologic history, as well as for observable selection bias using propensity score weighting and for within-center correlation using generalized estimating equations.Of the 155 infants in the study (81 girls and 74 boys; median age, 4.7 months [interquartile range, 3.0-7.1 months]), those treated with levetiracetam (n = 117) were older at the time of the first seizure than those treated with phenobarbital (n = 38; median age, 5.2 months [interquartile range, 3.5-8.2 months] vs 3.0 months [interquartile range, 2.0-4.4 months]; P.001). There were no other significant bivariate differences. Infants treated with levetiracetam were free from monotherapy failure more often than those treated with phenobarbital (47 [40.2%] vs 6 [15.8%]; P = .01). The superiority of levetiracetam over phenobarbital persisted after adjusting for covariates, observable selection bias, and within-center correlation (odds ratio, 4.2; 95% confidence interval [CI], 1.1-16; number needed to treat, 3.5 [95% CI, 1.7-60]).Levetiracetam may have superior effectiveness compared to phenobarbital for initial monotherapy of nonsyndromic epilepsy in infants. If 100 infants who received phenobarbital were instead treated with levetiracetam, 44 would be free from monotherapy failure instead of 16 by the estimates in this study. Randomized clinical trials are necessary to confirm these findings.

Intracranial hemorrhage accounts for about 50% of all pediatric stroke. Studies of term infants with intracranial hemorrhage have shown favorable motor and cognitive outcome. The goal of this study was to examine the risk of developing epilepsy in full-term infants with intracranial hemorrhage. A retrospective study was performed of term neonates (greater than or equal to 37 weeks gestation) with intracranial hemorrhage and confirmed seizures. Fifteen patients with intracranial hemorrhage and neonatal seizures were identified. Four patients did not have follow-up information beyond the neonatal period (1 death, 3 lost to follow-up after initial clinic visit). The average follow-up period for the remaining 11 patients was approximately 22 months. Ten out of the 11 patients (91%) who were followed were seizure-free and off antiepileptic medications. One patient required a ventriculoperitoneal shunt and subsequently developed infantile spasms. The authors found that overall outcome was favorable with respect to development of epilepsy.

Pyridoxine-dependent epilepsy is a rare, autosomal recessive, treatable cause of neonatal seizures. Genetic testing can confirm mutations in the ALDH7A1 gene, which encodes antiquitin. To avoid delays in initiating treatment while awaiting confirmatory genetic testing, it is recommended that all neonates with unexplained seizures should receive trial of intravenous (IV) pyridoxine to assess for responsiveness. However, oral pyridoxine is not commonly continued in the absence of the typical EEG changes. Two cases are presented that highlight the potential inadequacy of this single-step approach. One neonate ultimately diagnosed with pyridoxine-dependent seizures had no EEG changes after administration of IV pyridoxine. In contrast, another neonate who did not have this diagnosis had profound EEG changes after pyridoxine administration. We present 2 cases that highlight the difficulties in using initial EEG response to IV pyridoxine in establishing a diagnosis of pyridoxine-dependent seizures in the neonate. Given the availability of biochemical markers and gene testing, we suggest that oral pyridoxine treatment should be continued until biochemical and/or genetic testing has confirmed the presence or absence of pyridoxine-dependent epilepsy.

OBJECTIVE: Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of SCL6A1-mutated patients.METHODS: We collected 24 SLC6A1 probands and 6 affected family members. Four previously published cases were included for further electroclinical description. In total, we reviewed the electroclinical data of 34 subjects.RESULTS: Cognitive development was impaired in 33/34 (97%) subjects; 28/34 had mild to moderate ID, with language impairment being the most common feature. Epilepsy was diagnosed in 31/34 cases with mean onset at 3.7 years. Cognitive assessment before epilepsy onset was available in 24/31 subjects and was normal in 25% (6/24), and consistent with mild ID in 46% (11/24) or moderate ID in 17% (4/24). Two patients had speech delay only, and 1 had severe ID. After epilepsy onset, cognition deteriorated in 46% (11/24) of cases. The most common seizure types were absence, myoclonic, and atonic seizures. Sixteen cases fulfilled the diagnostic criteria for MAE. Seven further patients had different forms of generalized epilepsy and 2 had focal epilepsy. Twenty of 31 patients became seizure-free, with valproic acid being the most effective drug. There was no clear-cut correlation between seizure control and cognitive outcome. Electroencephalography (EEG) findings were available in 27/31 patients showing irregular bursts of diffuse 2.5-3.5 Hz spikes/polyspikes-and-slow waves in 25/31. Two patients developed an EEG pattern resembling electrical status epilepticus during sleep. Ataxia was observed in 7/34 cases. We describe 7 truncating and 18 missense variants, including 4 recurrent variants (Gly232Val, Ala288Val, Val342Met, and Gly362Arg).SIGNIFICANCE: Most patients carrying pathogenic SLC6A1 variants have an MAE phenotype with language delay and mild/moderate ID before epilepsy onset. However, ID alone or associated with focal epilepsy can also be observed.

Summary Objective Hypsarrhythmia is the classic interictal electroencephalographic pattern associated with infantile spasms, and characterized by high voltage, disorganization, and multifocal independent epileptiform discharges. Given this seemingly simple definition, one might expect excellent interrater reliability (IRR) in the identification of this pattern. Alternatively, it may be argued that assessments of voltage and disorganization are fairly subjective, and thus quite challenging in borderline cases. We sought to test the IRR of hypsarrhythmia assessment in a systematic fashion. Methods Six blinded pediatric electroencephalographers from four centers reviewed 22 electroencephalography (EEG) samples from patients with infantile spasms. Each sample was 5 min in duration and included only wakefulness. Raters determined if each EEG was abnormal and if hypsarrhythmia was present/absent, and characterized relevant features: voltage, organization, epileptiform discharges, slowing, interictal attenuations, symmetry, and synchrony. In addition, raters indicated their level of confidence for each assessment. Multirater kappa statistics (κ) were calculated for the assessment of hypsarrhythmia and each feature. Results Although IRR was favorable in determining whether a study was normal or abnormal (κ = 0.89), reliability was unfavorable for assessment of hypsarrhythmia (κ = 0.40), modified hypsarrhythmia (κ = 0.47), high voltage (κ = 0.37), disorganization (κ = 0.22), multifocal epileptiform discharges (κ = 0.68), interictal voltage attenuations (κ = 0.21), slowing (κ = 0.20), asymmetry (κ = 0.26), and asynchrony (κ = 0.08). Despite generally unsatisfactory interrater agreement, raters consistently reported high confidence in assessments. Significance This study contradicts the view that hypsarrhythmia assessment is straightforward. Even small variability in the identification of hypsarrhythmia has potentially deleterious consequences for clinical care, as its presence or absence impacts decisions to pursue high-risk and high-cost therapies. These inconsistencies may similarly confound studies in which abolition of hypsarrhythmia is an outcome measure. There is a great need for practical, reliable, and unbiased measures of hypsarrhythmia.

The Neurology ® Resident & Fellow page was launched in 2004 by Berch Griggs, then the Editor-in-Chief of Neurology , and Karen Johnston, Associate Editor. The Editors envisioned a forum for trainees and educators to publish articles on topics relevant to residency and fellowship. Articles in this experimental page included clinical reviews and education research projects, as well as commentaries on practice, ethics, teaching, history, and international training experiences. By 2015, under the guidance of Mitch Elkind, former Section Editor, the “Page” had become a “Section,” articles appeared weekly, projects like Podcasts and a Writing Award were introduced, and a growing team of trainee editorial team members were recruited. Now with over a decade of accomplishment, the Resident & Fellow Section (RFS) continues its growth, expansion, and vision for the future. John Millichap, a former editorial team member and the new RFS Associate Editor, assumed leadership of the section as of July 1, 2015. He is joined by Deputy Associate Editor Roy Strowd, another former editorial team member.

SummaryObjective Infantile spasms (IS) represent a severe epileptic encephalopathy presenting in the first 2 years of life. Recommended first-line therapies (hormonal therapy or vigabatrin) often fail. We evaluated response to second treatment for IS in children in whom the initial therapy failed to produce both clinical remission and electrographic resolution of hypsarhythmia and whether time to treatment was related to outcome. Methods The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of IS. Children were considered nonresponders to first treatment if there was no clinical remission or persistence of hypsarhythmia. Treatment was evaluated as hormonal therapy (adrenocorticotropic hormone [ACTH] or oral corticosteroids), vigabatrin, or “other.” Standard treatments (hormonal and vigabatrin) were compared to all other nonstandard treatments. We compared response rates using chi-square tests and multivariable logistic regression models. Results One hundred eighteen infants were included from 19 centers. Overall response rate to a second treatment was 37% (n = 44). Children who received standard medications with differing mechanisms for first and second treatment had higher response rates than other sequences (27/49 [55%] vs. 17/69 [25%], p < 0.001). Children receiving first treatment within 4 weeks of IS onset had a higher response rate to second treatment than those initially treated later (36/82 [44%] vs. 8/34 [24%], p = 0.040). Significance Greater than one third of children with IS will respond to a second medication. Choosing a standard medication (ACTH, oral corticosteroids, or vigabatrin) that has a different mechanism of action appears to be more effective. Rapid initial treatment increases the likelihood of response to the second treatment.

Investigators at Departments of Child Neurology, Neuroscience, Biostatistics, Marmara University, Istanbul, Turkey studied the parameters for prediction of epileptiform abnormalities in the EEG of 148 children diagnosed with ADHD, according to DSM-IV criteria, aged between 6 and 13 years (mean 8.76 +/- 1.26; 25.7% female). Wake and sleep EEGs lasting about one hour were obtained in 89.2% patients and a WISC-R in 100%.

Investigators from Lithuanian University of Health Sciences, Kaunas, evaluated the effects of neuropsychological activation (NPA) tasks on epileptiform discharges (ED) in adolescents with idiopathic generalized epilepsy (IGE) and in comparison with hyperventilation and photic stimulation.

The authors determined the frequency of epileptiform discharges in the electroencephalogram (EEG) of a cohort of children and adolescents referred to a neurology specialty clinic for evaluation of attention-deficit disorders. Of 624 records, 461 (73.9%) were normal and 163 (26.1%) abnormal. Of abnormal EEGs, 70 (42.9%) had focal epileptiform discharges only, 68 (41.7%) had generalized epileptiform discharges only, and 19 (11.6%) had both independent focal and generalized spikes. Focal spikes were localized chiefly in central, frontal, and temporal regions. Of 163 records with abnormalities, 154 (94.5%) were sleep deprived and 159 (97.5%) were sleep records. One-quarter of the nonepileptic children evaluated for attention-deficit disorder have epileptiform discharges in the EEG, and just more than half are focal. Sleep-deprived sleep is essential to exclude epileptiform abnormalities. The utility of the EEG in the management of attention-deficit disorders and selection of stimulant or nonstimulant medication deserves further study.

In “Smoking cessation and outcome after ischemic stroke or TIA,” authors Epstein et al. assessed whether smoking cessation after an ischemic stroke or TIA improves outcomes. Following a prospective observational cohort study of 3,876 nondiabetic men and women enrolled in the Insulin Resistance Intervention After Stroke trial, they found that cessation of cigarette smoking after an ischemic stroke or TIA was associated with significant health benefits over 4.8 years. Commenting on the study, Dr. Munakomi points out that the health hazards of passive smoking may have been neglected in the study. He explains that environmental tobacco smoke and secondhand smoking increase the risk of stroke and suggests implementing strict heath regulation acts to address this issue.

Infantile spasms are the defining seizures of West syndrome, a severe form of early life epilepsy with poorly-understood pathophysiology. We present a novel comparative analysis of infants with spasms versus other seizure-types and identify clinical, etiological, and molecular-genetic factors preferentially predisposing to spasms. We compared ages, clinical etiologies, and associated-genes between spasms and non-spasms groups in a multicenter cohort of 509 infants (

Dravet syndrome (DS), previously known as severe myoclonic epilepsy in infancy (SMEI), is an epileptic encephalopathy that presents with prolonged seizures in the first year of life. The seizures often occur with fever or illness, and are frequently initially categorized as febrile seizures. The correct diagnosis of DS and appropriate follow-up are typically delayed. The EEG is normal at onset, and neuroimaging reveals no structural lesion. Early development is normal, but signs of regression appear in the second year of life and are often accompanied by convulsive status epilepticus, alternating hemiconvulsions, and myoclonic seizures. Diagnosis can be confirmed by genetic testing that is now available, and shows mutations within the SCN1A gene. Early recognition and diagnosis of DS and management with appropriate anticonvulsants and treatment plan may reduce the seizure burden and improve long-term developmental outcome.

Respiratory syncytial virus is a common cause of infection in children. The authors summarize the clinical and diagnostic features of 9 patients admitted to the pediatric intensive care unit with neurological consultation. Patients were aged 5 weeks to 3 years. Four had seizures, 4 had cardiac arrest, and 1 had hypertonia. Results of brain magnetic resonance imaging in 5 patients was abnormal in 1. Cerebrospinal fluid in 4 patients showed elevated protein in 1. Serum sodium was low in 2 patients and normal in 7. Electroencephalograms in 8 patients were abnormal in 7. Increased risk of neurological complications of respiratory syncytial virus should be considered in any patient with documented infection requiring intensive care. Clinical manifestations may include seizures, encephalopathy, and abnormal neurological examination. The authors’ data suggest that the electroencephalogram provides a sensitive method for detection of neurological insult in this group of patients.

The management of febrile seizures is reviewed, with emphasis on methods of investigation and treatment of associated infections. Records of 100 consecutive febrile seizure patient-visits were examined retrospectively at an East Carolina University-affiliated hospital. Causes of fever and infection, viral and bacterial studies, antipyretic, antibiotic, and antiviral treatments, and indications for lumbar puncture were analyzed. Febrile seizures were first episodes in 64, simple in 76, and complex in 23 (prolonged, at 30-60 minutes, in 4). The mean age was 20 months. Viral studies in 26 patients were positive in 9 (35%). Bacterial cultures in 100 were positive in 5%, none from CSF. Antibiotics were prescribed in 65%, and antipyretics in 89%. Lumbar puncture was performed in 14 patients; 11 had complex seizures, and 3 simple. Of simple seizure patients, none was aged

Spinal cord infarction is uncommon and usually presents with sudden onset of paralysis and sensory disturbances. A variety of causes are described, but rarely with multiple factors involved. We report a case of a 63-year-old man with a history of diabetes mellitus, hypertension, and osteoarthritis who presented with acute onset of chest pain, numbness, and weakness associated with episodic hypotension. He had incomplete tetraplegia and was areflexic without spasticity. Pain and temperature sensations were impaired below the C7 dermatome and absent below the T4 dermatome bilaterally. Proprioception and vibration sensations were diminished on the right below the C6 dermatome. Magnetic resonance imaging showed spinal cord infarction affecting C6–T3 segments, and severe cervical and lumbar spine degenerative changes. This case illustrates an unusual presenting symptom of spinal infarction, the need to identify multiple risk factors for spinal cord infarction, and the importance of optimal preventive therapy in patients at risk.

In 2004, Berch Griggs, then the Editor-in-Chief of Neurology ®, and Karen Johnston, Associate Editor, launched the Resident & Fellow Page as a forum for trainees and educators to publish articles on topics relevant to residency and fellowship.1 Articles in this experimental page included clinical reviews and education research projects, as well as commentaries on practice, ethics, teaching, history, and international training experiences. By 2014, 10 years later, the “Page” had become a solidified “Section” of the journal with articles appearing weekly and ongoing projects like Podcasts and the Writing Award supported by a diverse group of resident and fellow editorial team members. In this decade, Neurology also enhanced reader access by adding a mobile version and an iPad® app. In 2015, we begin our second decade of the Resident & Fellow section (RFS) with a number of new initiatives and projects already underway.

Hypsarhythmia was originally spelled with one ‘r’ by Drs Frederick and Erna Gibbs when they coined the term in 1952.

To determine whether certain characteristic electroencephalography (EEG) features are indicative of a genetic cause in early-life epilepsy.We enrolled a total of 100 patients with infantile-onset (3 years) epilepsy due to known genetic cause (n = 50) and nongenetic cause (acquired, structural, or unknown, n = 50). The genetic group was classified into synaptopathies, channelopathies, mTOR (mammalian target of rapamycin)-opathies, and chromosomal abnormalities. The nongenetic group included epilepsy of unknown cause and structural abnormalities such as brain tumor, focal cortical dysplasia and encephalomalacia. The clinical features, magnetic resonance imaging, and video EEG obtained before 3 years of age and again at follow-up were reviewed. Specifically, the background rhythms and patterns of interictal epileptiform discharges were analyzed to define the EEG characteristics.The genetic group was more likely to have seizure recurrence beyond infancy and significant developmental delay (P .01). The genetic and nongenetic groups showed different EEG patterns in the initial EEGs that persisted in follow-up EEGs. Diffuse slowing with pleomorphic focal/multifocal epileptiform discharges were present more often in the genetic (86%) compared with the nongenetic group (20%) in the initial EEGs (P .01). The last available follow-up EEG features were similar (81% in genetic versus 17% in nongenetic) to the EEG performed prior to 3 years of age.Our findings suggest a simple guide for genetic screening in children with early-onset epilepsy. Genetic testing may be indicated and useful in infants with delayed development, no obvious cause, and significant EEG background slowing with pleomorphic focal or multifocal epileptiform discharges.

“Practice Current: An interactive exchange on controversial topics” is a new section that debuts in this issue of Neurology: Clinical Practice ( NCP ). The idea was conceived by Luca Bartolini, MD, editorial team member of the Resident & Fellow Section of Neurology ®, and developed in collaboration with the Editors of NCP . Practice Current aims to identify and discuss difficult clinical scenarios and diseases with conflicting or insufficient evidence regarding diagnosis or treatment. The topics will be selected based on relevance to clinical practice.

Febrile seizure is defined as a seizure associated with a febrile illness without a history of afebrile seizure or evidence of an acute central nervous system infection or other insult. Febrile status epilepticus is defined as a febrile seizure with duration greater than 30 minutes. Febrile seizures are the most common seizure type under age 5 years. Febrile status epilepticus is associated with an increased risk of temporal lobe epilepsy with evidence of acute hippocampal injury. Primary HHV-6B infection is a common cause of fever with both febrile seizures and febrile status epilepticus. Reactivated HHV-6B infection following stem cell transplantation has been associated with hippocampal injury and seizures in the context of limbic encephalitis. If the suspected association between HHV-6B infection and temporal lobe epilepsy is proven, then future studies may focus on therapy for HHV-6B infection for the prevention of epilepsy in these children.

Objective: To advance the understanding of KCNQ2 encephalopathy genotype–phenotype relationships and to begin to assess the potential of selective KCNQ channel openers as targeted treatments. Methods: We retrospectively studied 23 patients with KCNQ2 encephalopathy, including 11 treated with ezogabine (EZO). We analyzed the genotype–phenotype relationships in these and 70 previously described patients. Results: The mean seizure onset age was 1.8 ± 1.6 (SD) days. Of the 20 EEGs obtained within a week of birth, 11 showed burst suppression. When new seizure types appeared in infancy (15 patients), the most common were epileptic spasms (n = 8). At last follow-up, seizures persisted in 9 patients. Development was delayed in all, severely in 14. The KCNQ2 variants identified introduced amino acid missense changes or, in one instance, a single residue deletion. They were clustered in 4 protein subdomains predicted to poison tetrameric channel functions. EZO use (assessed by the treating physicians and parents) was associated with improvement in seizures and/or development in 3 of the 4 treated before 6 months of age, and 2 of the 7 treated later; no serious side effects were observed. Conclusions: KCNQ2 variants cause neonatal-onset epileptic encephalopathy of widely varying severity. Pathogenic variants in epileptic encephalopathy are clustered in “hot spots” known to be critical for channel activity. For variants causing KCNQ2 channel loss of function, EZO appeared well tolerated and potentially beneficial against refractory seizures when started early. Larger, prospective studies are needed to enable better definition of prognostic categories and more robust testing of novel interventions. Classification of evidence: This study provides Class IV evidence that EZO is effective for refractory seizures in patients with epilepsy due to KCNQ2 encephalopathy.

Investigators at Sapienza University of Rome, Italy, describe 12 children with Panayiotopoulos syndrome (PS) misdiagnosed as gastroesophageal reflux disease (GERD).

Epileptologists from Children's Hospital, Boston, and UCLA, California, discuss approaches to the differential diagnosis of Lennox Gastaut syndrome (LGS) and identification of a possible underlying etiology.

Epileptologists at University of Toronto and University of Saskatchewan, Canada, evaluated the complexity of epilepsy patients transitioned from child to adult care between tertiary centers compared to patients transferred from the community.

Investigators at the Massachusetts General Hospital, Boston, MA, and Universitat Autonoma de Barcelona, Spain, assessed the prevalence and characteristics of arachnoid cysts in a cohort of 220 patients with tuberous sclerosis complex (TSC).

Investigators on behalf of the MS Study Group of the Italian Neurological Society performed a third cognitive assessment on 48 of 63 patients with childhood or juvenile MS in the original cohort and compared with 46 healthy controls.

Investigators at Nihon University School of Medicine, Tokyo, Japan, report two patients with Wolf-Hirschhorn syndrome (WHS) who have a strong affinity for music, not previously described as a feature of this syndrome.

Over the past 10 years, the Neurology ® Resident & Fellow Section (RFS) has served as an outlet for articles and other journal-related activities relevant to trainees. The RFS was founded in 2004 by Drs. Karen Johnston and Robert Griggs with a focus on academic topics such as training, practice, ethics, teaching, and international training experiences.1 The initial goals were met and superseded as subsections have gradually evolved to cover current areas, including Emerging Subspecialties in Neurology, Clinical Reasoning, Right Brain, Child Neurology, Pearls & Oy-sters, International Issues, Education Research and Initiatives, Teaching Neuro Images (including both static images and videos), and Media and Book Reviews. In addition, submissions have grown in number and quality from 12 in 2004 to 481 in 2013, with a current acceptance rate at approximately 30% (figure). A full listing of the different subsections and other activities of the RFS can be found at . Two excellent examples of articles from the RFS can be found in this issue of Neurology .

Staff members at the Mayo Clinic, Rochester, MN, and University of Iowa Children's Hospital, Iowa City, report a healthy 22-year-old man with a focal encephalitis following varicella-zoster virus (VZV) reactivation without rash, triggered by varicella vaccination required for employment in a hospital

Investigators at the Taipei Medical University Hospital and other centers in Taiwan conducted a case-control study in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n = 61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n = 44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia.

Investigators at Fujita University School of Medicine, Toyoake, Aichi, Japan, performed a nation-wide survey to determine the incidence and clinical features of rotavirus-associated encephalitis/encephalopathy (RV-AE) and sudden unexpected death (SUD) in Japan.

Investigators at University of Toronto, Canada, report detection of atypical (dysplastic) neuronal elements in 4 of 5 teratomas resected from cases with NMDAR encephalitis but not in 39 controls.

Investigators at University of California, San Francisco, and other centers, report a case of leptospirosis in a 14-year-old boy with severe combined immunodeficiency.

Investigators at Bambino Genu Children's Hospital, Rome, and multiple additional centers in Italy conducted a retrospective and prospective study of clinical manifestations at diagnosis and during follow-up of 228 patients with 22q11.2 deletion syndrome.

Investigators at the Division of Emergency Medicine, Children's National Medical Center, Washington, DC, and ten additional US centers in the Pediatric Emergency Care Applied Research Network (PECARN), conducted a double-blind, randomized clinical trial comparing the efficacy and safety of lorazepam and diazepam in the treatment of generalized convulsive status epilepticus (SE) in children aged 3 months to younger than 18 years.

Investigators from the Epilepsy Center, Lurie Children's Hospital of Chicago, and Yale School of Medicine, New Haven, CT, examined the possible association between long-term seizure outcome of childhood absence epilepsy (CAE) and the initial treatment with ethosuximide (ESM) or valproic acid (VPA).

Investigators at the National Institute of Mental Health and Neurosciences, Bangalore, India, conducted a retrospective analysis of semiologic patterns of psychogenic non-epileptic seizures (PNES) diagnosed by video EEG in 56 children aged < 18 years (mean age 12.3 yrs; range 2-17 yrs).