Editor's Choice Collection

The Editor's Choice article for December is “Causes of new-onset seizures and their treatment in children with non-CNS malignancies: A retrospective study in a tertiary care center” by Fatima Jaafar. In this research paper, the authors retrospectively review charts of pediatric patients with non-CNS malignancies and seizures. Fifty-six patients were identified, primarily with acute lymphoblastic leukemia, lymphomas and sarcomas; 19 presented with status epilepticus and the etiologies included stroke, posterior reversible encephalopathy syndrome and metastasis. This study reminds readers that even patients with non-CNS tumors are at risk for seizures and may require longterm anti-seizure medications depending upon etiology.

The November 2022 Editor's Choice article is "Isolated Absent Septum Pellucidum: A Retrospective Study of Fetal Diagnosis and Postnatal Outcomes" by Elizabeth E.S. Pickup and colleagues. In this research article the authors retrospectively reviewed maternal-fetal dyads from 2012-19 for cases of absent septum pellucidum (ASP); both isolated and complex ASP cases were included, prenatally diagnosed and confirmed postnatal imaging. Few children with prenatally diagnosed isolated ASP had septo-optic dysplasia diagnosed postnatally. Overall, children with isolated ASP demonstrate better outcomes than children with complex ASP. Fetal magnetic resonance imaging is a useful tool to evaluate the septum pellucidum and may reveal additional abnormalities that can impact prognosis and affect prenatal counseling.

The October 2022 Editor’s Choice article is “Neurologic complications in children hospitalized with seizures and respiratory infections: A comparison between SARS-CoV-2 and other respiratory infections” by Grace Gombolay and colleagues. In this research paper the authors retrospectively reviewed the hospital courses of 883 admitted for seizures and the presence of viral respiratory infections including SARS-CoV-2, mycoplasma pneumoniae, other corona viruses (OC), influenza A and B, adenovirus, and parainfluenza 3 and 4. In these children, higher rates of stroke were observed in patients with SARS-CoV-2 than in patients with OC; similar rates of neurological symptoms were observed in patients with SARS-CoV-2 and those with influenza. Though the SARS-CoV-2 pandemic has abated somewhat with the advent of improved public health measures, vaccines and anti-viral therapies, future studies examining neurologic outcomes in children will determine if these measures have succeeded in reducing morbidity and mortality.

The September 2022 Editor's Choice article is "Characteristics of Moyamoya Syndrome in Pediatric Patients with Neurofibromatosis Type 1" by Stehanie Brosius Alonso and colleagues. In this research paper, the authors performed a meta-analysis and identified 152 pediatric patients with neurofibromatosis type 1 (NF1) and moyamoya syndrome (MMS) in the literature through 2020 and identified 19 similar patients from 1995-2020 at their own institution. In both the meta-analysis and institutional cohort, stroke was a significant source of morbidity in children with NF1 and MMS. Optic pathway tumors were more common in patients with MMS and the data suggests that a more aggressive form of MMS may exist in patients with NF1 less than 4 years of age and earlier screening of these patients may be indicated.

The August 2022 Editor's Choice article is "Influence of Gestational Diabetes and Pregestational Maternal BMI on the Brain of Six-Year-Old Offspring" by Jordi Manuello and colleagues. In this research paper the authors used a combination of support vectors machine and hierarchical clustering to investigate the potential presence of anatomical brain differences in a sample of 109 six-year-old children, born to mothers diagnosed with GD during pregnancy. Significant effects are visible in the brain of children born to mothers with GD associated with pregestational excess weight, especially overweight. No differences in children's brain were observed when considering those born to normal-weight mothers. Further study is required to correlate the imaging findings with clinical outcomes.

The July 2022 Editor's Choice article is "Autoimmune encephalitis in children" by Duriel Hardy. This review article provides a timely , comprehensive summary of the numerous autoimmune encephalitides which have been described since 1968, when N-methyl-D-aspartate (NMDA) receptor encephalitis was first described. The etiology, diagnosis, and treatment are reviewed and a practical algorithm on the approach to a pediatric patient with suspected autoimmune encephalitis (AE) included. In addition to the more familiar AEs like NMDA-R and myelin oligodendrocyte glycoprotein (MOG) encephalitis, the author discusses Ophelia syndrome, a limbic encephalitis associated with Hodgkin lymphoma, in which antibodies to the metabotropic glutamate receptor 5 (mGluR5) are often identified. This article will help clinicians quickly diagnose and treat these patients to prevent long-term sequelae of AEs and improve overall survival.

The June 2022 Editor's Choice article is "Reproductive Health Counseling in Adolescent Women With Epilepsy: A Single-Center Study" by Cheyenne Smith and colleagues. This research paper is a retrospective chart review to determine how many adolescent females with epilepsy at one center's pediatric neurology and epilepsy clinics from 2018 to 2020 received reproductive health counseling. The authors identified 219 visits from 89 individuals and found that a minority of adolescent women with epilepsy have documented reproductive health discussions, demonstrating a need for quality improvement projects to address this gap in care. This article is timely, as currently worldwide, and particularly in the US, the reproductive rights of women are in jeopardy.

The May 2022 Editor's Choice article is "The Phenomenology of Tics and Tic-Like Behavior in TikTok" by Alonso Zea Vera and colleagues. This research paper investigates the phenomenology of functional tic-like disorders due to the sharp uptick in cases reported in children during the SARS CoV-2 pandemic. The authors identified 100 most-viewed TikTok videos with #tourettes and randomly assigned them to primary reviewers trained in movement disorders. Coprolalia and copropraxia were the most common behaviors and many symptoms were atypical. There as good concordance among the reviewers. The authors conclude that the tic-like behaviors seen in TikToks were not consistent with Tourette's syndrome and could be misleading to the public. This article demonstrates yet another reason to increase mental health services for children and teens, adversely affected by the isolation and trauma of the events of the past 2 years.

This month's Editor's Choice selection is "Multimodal Neurologic Monitoring in Children with Acute Brain Injury" by Jennifer Laws and colleagues. The authors of this comprehensive Review Article discuss existing invasive and non-invasive modalities to monitor neurologic function in children with acute brain injury. Traditionally intracranial pressure and more importantly cerebral perfusion pressure have been monitored intracranially, but optic nerve sheath diameter and near infrared spectroscopy may be non-invasive techniques to obtain similar data. Further study is required to validate some parameters but elucidation of physiologic pathways while simultaneously developing neuroprotective strategies, will ultimately lead to improved outcome in children with acute brain injury.

This month’s Editor’s Choice selection is “ Efficacy and Safety of Repetitive Intravenous Sodium Valproate in Pediatric Patients With Refractory Chronic Headache Disorders: A Retrospective Review” by Sara Pavitt and colleagues. The authors identified 45 pediatric patients from 2017-2020 admitted for intravenous VPA infusion for prevention of refractory chronic primary headache disorder. Patients were also switched to a new preventive agent. The regimen was well tolerated and while headache frequency remained stable, headache intensity and acuity were significantly reduced. The article provides hope for pediatric patients with chronic headaches. Further study is needed to resolve whether the VPA infusion alone, the addition of a new preventive agent or the combination helped these patients.

The February 2021 Editor’s Choice selection is Disorders of Neuronal Migration/Organization Convey the Highest Risk of Neonatal Onset Epilepsy Compared With Other Congenital Brain Malformations by Roxanne Simmons, MD and colleagues.

This research paper identifies 132 neonates from 2008-2019 with epilepsy-associated congenital brain malformations at a quaternary medical center. Patients with neuronal migration/organization disorders had the highest risk of both seizures and mortality. The study confirms the American Clinical Neurophysiology Society recommendations for neonatal continuous EEG monitoring and supports counseling for prenatal detection of these findings, though postnatal management of these patients requires more study.

This month’s Editor’s Choice selection is ”Leo Alexander’s Blueprint of the Nuremberg Code,” by Pedro Weisleder. Decades after their conclusion, we remain captivated by the Nuremberg trials as well as horrified by the acts that led to them. The lasting legacy of the Nazi Doctors’ Trial was the initial characterization of the concepts that continue to define humane and ethical research on human beings – the Nuremberg Code. As is evident in Weisleder’s article, Leo Alexander was the driving force behind the Nuremberg Code, and humankind owes him a debt of gratitude.

This month’s Editor’s Choice selection is “Stroke Following Acute Chest Syndrome in a Child with Sickle Cell Disease: A Possible Novel Etiology” by Nicole Kendel and colleagues. This brief report makes a persuasive argument for a new mechanism for stroke in some individuals with sickle cell disease – embolism of pulmonary vascular thromboses following acute chest syndrome. Their patient did not have the customary cerebral artery vasculopathy of sickle cell disease, nor did he have a coagulopathy or evidence of intracardiac shunting. The occurrence of the child’s stroke just after recovery from acute chest syndrome and the absence of other stroke mechanisms contributes to the plausibility of their hypothesis. If confirmed, this observation could have important implications for the management of acute chest syndrome in individuals with sickle cell disease.

This month’s Editor’s Choice selection is “Family-Centered Care for Children and Families Impacted by Neonatal Seizures: Advice From Parents” by Monica E. Lemmon and colleagues. The parents of 310 neonates with acute symptomatic seizures completed family well-being surveys at 12, 18 and 24 months corrected gestational age. Some of these parents also provided recommendations to physicians about optimizing communication and improving family support. We physicians likely overestimate our own effectiveness in communicating with families of critically ill children. Gaining a better sense of what parents need and value is a good place to start improving.

This month’s Editor’s Choice selection is “Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations” by Darcy Krueger and colleagues. This article represents a consensus of worldwide tuberous sclerosis complex experts and is the first update of the diagnostic criteria and management recommendations since 2013, when the previous recommendations and criteria appeared in Pediatric Neurology. Clinical diagnostic criteria remain useful even in this age of genetic testing, because the results are immediate and the cost is negligible. The correlation between the criteria and the results of DNA testing is excellent though of course not flawless. Similarly, the expert recommendations about specific therapies and the utility of surveillance testing to facilitate early diagnosis of complications are invaluable.

This month’s Editor’s Choice selection is “The Names of Things: The 2018 Bernard Sachs Lecture” by William B. Dobyns. This article about the genetics of brain malformations evolved from Dobyns’ Bernard Sachs Lecture at the 2018 Child Neurology Society meeting. Our understanding of the pathogenesis of these brain lesions has increased dramatically during the three-plus decades that Dobyns has worked in the field. Equally captivating, however, is the inspiring personal and scientific journey that is captured here, the story of how curiosity, persistence, and collaboration led to major discoveries.

This month’s Editor’s Choice selection is “Consensus Statement for the Management and Treatment of Sturge-Weber Syndrome: Neurology, Neuroimaging, and Ophthalmology Recommendations” by Sara Sabeti and colleagues. For conditions that have not been subjected to extensive clinical trials, a consensus of expert opinion often represents a reasonable substitute for better evidence-based information. Such statements are particularly useful for highly variable and difficult-to-manage disorders such as Sturge-Weber syndrome. Few of us have sufficient personal experience with this disorder to ensure optimal decision making, but these consensus recommendations from experts in the field should help.

This month’s Editor’s Choice selection is “Placental histological features and neurodevelopmental outcomes at two years in very low birth weight infants” by Arsenio Spinillo and colleagues of Pavia, Italy. The article documents a correlation between survival or developmental outcome and placental abnormalities such as chorioamnionitis, evidence of abnormal perfusion, and intravillous hemorrhage in a cohort of 595 very low birthweight babies. The placenta is the baby’s lifeline during gestation, and it is disappointing that, until relatively recently, little effort has been made to study the placenta’s contribution to the problems of neonates. One can only hope that this article reflects a trend.

This month’s Editor’s Choice selection is “Amelioration of Levetiracetam-Induced Behavioral Side Effects by Pyridoxine. A Randomized Double Blind Controlled Study” by Adel Mahmoud and colleagues. For years many of us have recommended the daily administration of pyridoxine (vitamin B6) for children with behavioral side effects related to levetiracetam. Pyridoxine seemed to be effective in some of these children, but until now the objective evidence supporting its use was limited. This randomized trial demonstrated a significant benefit from pyridoxine compared with placebo. The trial enrolled 105 children, which is not a huge number. But a small randomized, placebo-controlled trial is far better than the past anecdotal approach.

This month’s Editor’s Choice selection is “Early Identification of Cerebral Palsy using Neonatal MRI and General Movements Assessment in a Cohort of High-Risk Term Neonates” by Hannah C. Glass and colleagues of San Francisco. The authors prospectively followed 58 children at risk for cerebral palsy for two years after each individual underwent magnetic resonance imaging as a neonate and a movement assessment scale at three months. Normal myelination of the posterior limb of the internal capsule as a neonate and normal fidgety movements at three months of age were negative predictors of later cerebral palsy. The study is timely, because two other articles in this issue highlight the general lack of high-grade evidence supporting the assessment and treatment of very young individuals with cerebral palsy. Glass and colleagues may need to study a larger cohort in order to draw definitive conclusions, but their study is a step in the right direction.

This month’s Editor’s Choice selection is “Extent of leptomeningeal capillary malformation is associated with severity of epilepsy in Sturge-Weber syndrome” by Sugano and colleagues. The authors analyzed the magnetic resonance imaging results of 112 individuals with Sturge-Weber syndrome and precisely categorized the location of each person’s leptomeningeal malformation. They then compared the location of the brain lesion to clinical details such as age at seizure onset, seizure type, response to seizure treatment, cognitive decline, and electroencephalography findings. Individuals with bilateral and hemispheric had earlier seizure onset, more frequent seizures, and more episodes of status epilepticus than patients with lobar or multilobe lesions. Although it may seem intuitive that individuals with more extensive brain lesions would experience more severe clinical manifestations, this study’s large cohort size and methodical characterization of the imaging studies provide convincing proof.

This month’s Editor’s Choice selection is “Early-onset Developmental and Epileptic Encephalopathies of Infancy: An Overview of the Genetic Basis and Clinical Features” by Nadine Morrison-Levy and her Canadian colleagues. The discovery of numerous genetic causes of early-onset neurological disorders in recent years has revolutionized our approach to these individuals. It is estimated that over three-fourths of the infants with developmental and epileptic encephalopathies can be traced to genetic disorders. This review contains a wealth of useful information on this fast-developing topic.

This month’s Editor’s Choice selection is “EEG Technologist Interrater Agreement and Interpretation of Pediatric Critical Care EEG” by Stephanie Ahrens and colleagues. Prolonged electroencephalography recording is being used more and more frequently to monitor critically ill children, but for this approach to be maximally effective, seizures and other treatable abnormalities must be quickly identified. The EEG technician plays a pivotal role in the monitoring process, because their real-time recognition an abnormality usually leads to more formal review of the study by an electroencephalographer. The qualifications and experience level of the technicians can vary widely even within the same institution, and until now there has been no systematic effort to determine the effectiveness of this technician gate-keeper function. This article is an important first step toward filling this void.

This month’s Editor’s Choice selection is “An Objective Structured Clinical Exam of Communication Skills for Child Neurology Residents” by Albert et al. Although we try to base clinical decisions on sound scientific evidence, our teaching methods often lack the same kind of data-driven, rigorous approach. Supported by a grant from the American Board of Psychiatry and Neurology, Albert and colleagues employed simulated patients in a sophisticated clinical simulation center to develop a series of standardized clinical encounters emphasizing communication skills for child neurology residents. This article summarizes their three-year project and shares their standardized patient encounters as supplemental files. This article should be required reading for anyone who teaches residents.

This month’s Editor’s Choice selection is “Sarnat Grading Scale for Neonatal Encephalopathy after 45 Years: An Update Proposal” by Sarnat et al. Forty-five years ago Sarnat and Sarnat developed a scale to objectively characterize the severity of encephalopathy in neonates. The Sarnat Scale was quickly adopted and remains an important tool for both clinical assessment and research purposes. Much has changed in the last 45 years, including new diagnostic techniques and a deeper understanding of the pathophysiology of neonatal encephalopathy. In this article, Sarnat and colleagues update the original Sarnat Scale, maintaining its original clinical focus while acknowledging the need to use imaging in parallel. Sarnat’s aside comments about the development of the original scale are also fascinating. Few of us would have been willing to personally perform electroencephalograms during the evenings when the machines were free in the name of research. And despite the enormous influence of the Sarnat Scale for almost half a century, the manuscript was rejected by a pediatric journal because it was considered too technical for pediatricians and neonatologists. With this update, the Sarnat Scale should be good for the next half century.

This month’s Editor’s Choice selection is “Diversifying Child Neurology: Developing a Workforce That Reflects the Patients and Families for Whom We Care” by Nina F. Schor. Almost everyone acknowledges that increasing diversity is an admirable goal, but well-meaning efforts over the years have more often than not fallen short of their goals, and it can be difficult to know where to begin. Refreshingly, Schor doesn’t claim to have all of the answers, but her thoughtful commentary is a good place to begin. Here she makes a plausible case that one major reason for the ongoing lack of racial diversity in clinical neuroscience can be traced to the paucity of neuroscience programs, and hence role models, during the formative professional careers of the underrepresented groups. This programmatic deficiency, in turn, likely stems from an ongoing lack of institutional support. So here is a thoughtful essay bolstered with some data that suggests good first steps toward improving diversity in the clinical neurosciences. Clearly any real progress will require more than a few required online training modules: it will require equity of institutional support and a commitment to provide neuroscience exposure much earlier in the curriculum.

This month’s Editor’s Choice Selection is “ACTH treatment of infantile spasms: Low-moderate vs high dose, natural vs synthetic ACTH. A retrospective study” by Raili Sylvia Riikonen and colleagues. The never-ending debate about how to treat infantile spasms is a controversy that seems to generate more heat than light. Professor Riikonen, however, has made substantial contributions to the study of infantile spasms for many years. By analyzing their older data, the authors were able to compare high and low dose natural ACTH and synthetic ACTH. The bottom line is that high dose natural ACTH is not more effective than low to moderate doses, and the synthetic ACTH was equally effective. These data once again suggest that synthetic ACTH is just as effective as natural ACTH and that the dosing may be less important than many people think.

This month’s Editor’s Choice selection is “Neuroprotection Care Bundle Implementation to Decrease Acute Brain Injury in Preterm Infants” by Murthy et al. These authors standardized the use of techniques designed to mitigate the risk of acute brain injury in extremely premature infants (less than 29 weeks’ gestational age) during the first three postnatal days. Examples of the changes included minimal handling, midline head position, and deferred cord clamping. After implementation of the care bundle, there was a notable reduction in various indicators that are associated with brain injury, such as the use of inotropes, the number of required fluid boluses, and the occurrence of a pneumothorax. The likelihood of death and severe brain injury diminished after the protocol was implemented. It can be difficult to apply clinical research observations in real clinical settings, especially when the proposed changes are subtle and interrelated. These authors demonstrated the tremendous value of standardizing care to routinely include techniques that would likely be neglected but for their protocol. There is a broader lesson here.

This month’s Editor’ Choice selection is “Intramuscular versus buccal midazolam for pediatric seizures: A Randomized Double-Blinded Trial” by Khalid Alansari et al. These authors conducted a double-blind, randomized trial of buccal versus intramuscular administration of midazolam in 150 children with status epilepticus. There was no significant difference between the two routes of administration, but this trial shows that intramuscular administration is a plausible option which may prove to be useful in some situations. This study illustrates the value of incorporating clinical research into day-to-day patient management.

This month’s Editor’s Choice selection is “Infantile Spasms: Outcome in Clinical Studies” by Raili Riikonen. While the diagnosis of infantile spasms is relatively straightforward, optimal management is often debated. Riikonen has long been at the forefront of infantile spasms research, and this superb article reflects insights from her many years of clinical and research experience. Readers will find this article extremely useful.

This month’s Editor’ Choice selection is “Evaluation of Diagnostic Criteria for Hashimoto Encephalopathy Among Children and Adolescents” by Ashley V. Adams and colleagues. The authors analyzed a series of children with Hasimoto encephalopathy and concluded that children are less likely to exhibit overt thyroid disease than adults with Hasimoto encephalopathy. Based on their findings, they propose modified diagnostic criteria for Hashimoto encephalopathy in children.

This month’s editor’s Choice selection is “Area Postrema: Fetal Maturation, Tumors, Vomiting Center, Growth, Role in Neuromyelitis Optica” by Sarnat et al. Sarnat and colleagues studied 12 normal fetal brains at six to 40 weeks’ gestation along with those from three infants aged three to 18 months and three infants with lesions to trace the morphological maturation of the area postrema. The article is beautifully written and illustrated with numerous histopathologic sections and radiographic images. Most of us have a sketchy understanding of this small part of the brain, but as Sarnat and colleagues so elegantly demonstrate, the area postrema plays an important role in numerous normal and abnormal brain functions.

This month’s Editor’s Choice selection is “Antecedents of Objectively Diagnosed Diffuse White Matter Abnormality in Very Preterm Infants” by Nehal Parikh and colleagues. Diffuse white matter abnormalities are common long-term sequalae of premature babies. These authors prospectively enrolled 110 neonates who were born at or below 31 weeks’ gestation. They performed brain magnetic resonance imaging at each baby’s term-equivalent age and collected clinical information for comparison. Bronchopulmonary dysplasia and retinopathy of prematurity were both associated with the occurrence of white matter abnormalities. One might argue that both of these conditions might simply reflect a more severe overall clinical course, one that might promote white matter injury in parallel. More intriguing is their suggestion that inflammation might constitute a common pathway that promotes white matter injury.

This month’s Editor’s Choice selection is “Cannabidiol Elevates mTOR Inhibitor Levels In Tuberous Sclerosis Complex Patients” by Daniel Ebrahimi-Fakhari and colleagues. These authors analyzed 25 patients with tuberous sclerosis complex who were being treated with both cannabidiol an mTOR inhibitor (either everolimus or sirolimus). They discovered that the trough levels of the mTOR inhibitor increased in 76% of the patients after starting cannabidiol. Elevation of the mTOR inhibitor levels after the addition of cannabidiol could result in either new side effects or in enhanced clinical efficacy of the mTOR inhibitor, either of which could be falsely attributed to the cannabidiol. This is a simple study, but one with practical clinically implications.

This month’s Editor’s Choice selection is “Characterizing Posterior Fossa Syndrome: A Survey of Experts” by Heather Conklin and colleagues. Most experienced clinicians are familiar with the posterior fossa (or cerebellar mutism) syndrome that occurs in some individuals following cerebellar surgery. The syndrome’s severity ranges from devastating to transient, and the variable clinical manifestations almost always include language impairment. The clinical variability of the posterior fossa syndrome make it difficult to categorize the patients for study. These authors used a survey of professionals who are knowledgeable about the syndrome to devise clinical diagnostic criteria for posterior fossa syndrome. Clinical diagnostic criteria are often useful tools for conditions with a spectrum of signs and symptoms but no reliable diagnostic markers, and these diagnostic criteria for the posterior fossa syndrome be a useful starting point for a better understanding of this syndrome.

This month’s Editor’s Choice selection is “Sleep wake disturbances after acquired brain injury in children surviving critical care” by Williams and colleagues. These authors address a common but poorly studied clinical problem – disruption of sleep following acquired brain injury. They prospectively studied 78 children with various kinds of acquired brain injury who were admitted to a critical care unit. Over half of these children experience persistent sleep disturbance, and the severity of the sleep disruption did not correlate precisely with the severity of brain injury. This problem will require additional study, but these authors have illustrated the magnitude of the problem and provided badly needed data.

This month’s Editor’s Choice selection is “Treatment of chorea in childhood” by Jonathan Mink. Chorea can be a distressing manifestation of a number of conditions, and few of us have the knowledge and experience to treat it effectively. Jonathan Mink is a consummate movement disorder specialist and a superb teacher of clinical medicine. His practical suggestions for treating chorea in children should be required reading for all physicians who care for children with neurological disorders.

This month’s Editor’s Choice selection is “Preventive antiepileptic treatment in tuberous sclerosis complex: A long-term, prospective trial” by Jozwiak and colleagues. There is increasing evidence that antiepileptic treatment prior to seizure onset in individuals at high risk for epilepsy may lessen the subsequent neurological dysfunction and minimize the epilepsy severity. In this article, Jozwiak and colleagues present multi-year follow-up data from 39 individuals with tuberous sclerosis complex, 14 of whom began taking vigabatrin after developing electrographic epileptiform discharges but prior to the onset of clinical seizures. The remaining 25 patients began treatment only after experiencing their first clinical seizure. The median IQ for the preventive treatment group was 94, versus 46 for those in the standard care group; half of the 14 children in the preventive group never developed clinical seizures in this eight year follow-up analysis, while there was only one seizure-free patient among the 25 standard care patients. Even after acknowledging the small cohort size, these results are stunning. These authors recently completed a larger multicenter trial (EPISTOP) in which children with tuberous complex were randomized to receive vigabatrin versus continued clinical observation after the detection of epileptiform discharges on electroencephalography. This trial seems to confirm the value of presymptomatic treatment, and if the outcome data from this larger trial mirror those presented here, there will be no doubt about the value of presymptomatic therapy. It is likely that these results will also be applicable for other individuals with a high likelihood of developing epilepsy at an early age.

This month’s Editor’s Choice selection is “Arterial Ischemic Stroke Secondary to Cardiac Disease in Neonates and Children” by Melissa Chung, et al. These authors analyzed 672 children with congenital or acquired heart disease and arterial ischemic stroke from the International Pediatric Stroke Study registry. Among other notable findings, 26% of the patients experienced a stroke around the time of a cardiac procedure, providing data to support the increased periprocedural stroke risk that we have long suspected. This remarkable article provides a wealth of other useful data, information that could only be collected via a large collaborative database.

This month’s editor’s choice selection is “Very high dose prednisolone before ACTH for treatment of infantile spasms: Evaluation of a standardized protocol” by Eliyan and colleagues. The authors analyzed a cohort of 102 children with infantile spasms who were treated with prednisolone via a standardized management protocol. Individuals who failed to respond to prednisolone were quickly switched to ACTH. The clinical response was confirmed by follow-up electroencephalography. Some 59% of the children who received prednisolone as their first line treatment responded favorably, and 33% of the individuals who failed to improve with prednisolone later responded to ACTH. Recurrence was common in both groups. This study adds to the growing body of evidence that, when adequately dosed, prednisolone represents a reasonably priced alternative to ACTH for treatment of infantile spasms.

This month’s Editor’s Choice selection is “Early Detection of Cerebral Palsy Using Sensorimotor Tract Biomarkers in Very Preterm Infants” by Nehal Parikh an colleagues in Cincinnati. Infants who are born very prematurely have a fifty-fold higher risk of cerebral palsy compared with term-born babies. It is generally agreed that children with cerebral palsy benefit from earlier therapy, but the diagnosis is not made in many of these children until age two years or later. These authors analyzed sensorimotor tracks with magnetic resonance imaging in very premature babies and suggest that changes in these structures can serve as a biomarker for subsequent development of cerebral palsy. Studies like this contribute to our understanding of the pathophysiology of cerebral palsy and might someday lead to earlier diagnosis and treatment of these individuals.

This month’s Editor’s Choice selection is “Premonitory Symptoms in Episodic and Chronic Migraine From a Pediatric Headache Clinic” by Howard Jacobs and Ann Pakalnis. Parents often describe sometimes subtle changes that herald their child’s migraine attack long before the onset of a typical aura or the start of headache. Until now we have had little solid information about the occurrence of these premonitory symptoms in children, but this article confirms that these symptoms are commonplace and suggests that they may be predictable enough in some children to allow earlier intervention. This article is also a good example of the useful, practical information that can result when we incorporate clinical research into our routine clinical practice. On a personal note, Dr. Jacobs was my friend and former colleague. His recent death is a great loss to his family, friends, and patients.

This month’s Editor’s Choice selection is “Physical growth of the contralateral cerebrum is preserved after hemispherotomy in childhood” by Patrick J. Pan and colleagues. These authors studied 11 children with hemimegalencephaly, Rasmussen encephalitis, or cerebral infarction who underwent hemispherotomy prior to age 12 years. Each child underwent a cranial MRI just prior to surgery and again at least three years after surgery. The volume of the contralateral hemisphere was calculated before and after surgery, and the growth rate compared to that of normal individuals. The individuals who underwent surgery earlier experienced the greatest post-operative volume increase in the contralateral hemisphere. The individuals with hemimegalencephaly underwent surgery at a young age and experienced a contralateral hemisphere growth rate that exceeded that of normal individuals. Individuals with Rasmussen encephalitis underwent surgery later and exhibited a contralateral hemisphere growth rate that was similar to that of normal individuals, while the children with a cerebral infarction underwent surgery later and experienced a growth rate that was less than that of normal individuals. Although the cohort is small, these findings seem to correlate with the frequent observation that earlier cerebral resection seems to allow more robust post-operative functional recovery.

This month’s Editor’s Choice selection is Joseph Volpe’s article “Dysmaturation of Premature Brain: Importance, Cellular Mechanisms and Potential Interventions.” Dr. Volpe makes a persuasive argument that a substantial portion of the neurological impairment that results from premature birth can be traced to ongoing disruption of brain maturation for a prolonged period after birth. Many of the cellular mechanisms that are responsible for this process have now been elucidated, including altered function of activated microglia and reactive astrocytes. Volpe synthesizes several lines of neurobiological evidence to demonstrate continuing postnatal disruption of brain maturation, and these data have enormous clinical implications: there is an extended postnatal interval during which the dysmaturation could be mitigated.

This month’s editor’s Choice selection is “Necessity of Intracranial Imaging in Infants and Children with Macrocephaly” by Megan A. Sampson et al. Macrocephaly is a common condition, but only occasionally does it herald a serious underlying neurological condition. Sampson and colleagues analyzed 169 children less than three years of age who underwent imaging with various modalities because of macrocephaly. Aside from the common finding of benign external hydrocephalus, only 13 of the children had abnormal imaging results, and only five of these had findings that were highly significant (two had hydrocephalus, two had subdural hemorrhage, and one had a combination of hydrocephalus and Chiari malformation). All five of these individuals had abnormal neurological findings or developmental delay. The authors conclude that imaging is not necessary in neurologically normal children with macrocephaly. While their conclusions will surprise few seasoned clinicians, having objective information is very useful.

This month’s Editor’s Choice selection is “Formation and Growth of the Child Neurology Society” by Steven Ashwal, Paul Rosman, and Kenneth Swaiman. Many of us marvel at the success of the Child Neurology Society, which in its nearly 50 year history has grown from a handful of academic child neurologists into a robust organization that promotes education, research, international outreach, and professional and social networking. Authors Rosman and Swaiman were founding members of the Society, and all three authors have served the organization for many decades. Here they lovingly tell the Society’s story to commemorate its approaching fiftieth anniversary. Given the Society’s role in molding the discipline of child neurology, this article is a valuable reference for historians as well as for anyone seeking information about the Society’s formation. Congratulation’s to the Child Neurology Society members on what will soon be a half century of steady progress.

This month’s Editor’s Choice selection is “Predictors of Primary Intracranial Hypertension in children, using a newly suggested opening pressure cutoff of 280 mm H2O” by Delaney and colleagues. These authors analyzed 374 individuals who were less than 21 years-of-age who underwent a diagnostic lumbar puncture specifically for suspected increased intracranial pressure. They compared the signs and symptoms of individuals whose opening pressure was greater than 200 mm H2O, those with pressure greater than 250 mm H2O, and those whose opening pressure was more than 280 mm H2O (the recently recommended new ceiling for the normal cerebrospinal fluid pressure range). Not surprisingly, individuals with higher opening pressures tend to exhibit more symptoms than those with values that are now considered to be normal. The subgroup with higher pressures had a somewhat different symptom profile, with more optic disc edema and a shorter duration of headache.

  • Predictors of Primary Intracranial Hypertension in Children Using a Newly Suggested Opening Pressure Cutoff of 280 mm H2O

    Atima C. Delaney, Aynslee Velarde, Marvin B. Harper, Alyssa Lebel, Assaf Landschaft, Michael Monuteaux, Gena Heidary, Amir A. Kimia
    Vol. 91, p27–33

This month’s Editor’s Choice selection is “Pediatric Infective Endocarditis and Stroke: A 13-years Single-center Review” by Cao et al. The incidence of infective endocarditis has declined dramatically since the advent of antibiotics, and the frequency of endocarditis-related stroke has declined in tandem. Here Cao and colleagues analyze 60 children with infective endocarditis, 43 of whom had congenital heart disease. Nine of the 60 children developed cerebrovascular complications, including five children with cerebral infarction, two with intracranial hemorrhage, one with a subarachnoid hemorrhage, and one with both hemorrhage and infarction. Despite the likely decline in the overall incidence of stroke related to infective endocarditis, stroke remains a common complication of infective endocarditis, especially in individuals with left-heart endocarditis.

This month’s Editor’s Choice selection is “Stroke In Pediatric Bacterial Meningitis: Population-Based Epidemiology” by Dunbar et al. Given the diffuse vascular inflammation that accompanies bacterial meningitis, it is not surprising that meningitis would promote intracranial thrombosis and stroke. The likelihood of stroke increases with the severity of the inflammation, so bacterial meningitis has a much greater stroke risk than does viral meningitis. Vaccines targeting common meningitis-causing organisms have dramatically reduced the incidence of bacterial meningitis, but the stroke risk persists in the children who develop meningitis. In this article, Dunbar and colleagues present a population-based retrospective analysis of children with confirmed bacterial meningitis who underwent magnetic resonance imaging. Ischemic stroke, often multifocal, was documented in 37% of these children. Children with infarction were more likely to exhibit persistent neurological deficits than those with only bacterial meningitis. This study determined the infarction risk and prognosis of children with bacterial meningitis. While the incidence of stroke due to meningitis may have declined, the risk of stroke among the remaining children with meningitis is even higher than earlier estimates.

This month’s Editor’s Choice selection is “Febrile Seizures and Epilepsy: Association With Autism and Neurodevelopmental Disorders in the Child and Adolescent Twin Study in Sweden” by Gillberg and colleagues. Using a structured, validated DSM-IV based interview, these authors analyzed 27,092 twins in the Child and Adolescent Twin Study of Sweden and the Swedish National Patient Register. They found an association between a diagnosis of epilepsy or febrile seizures and autism spectrum disorder, developmental coordination disorder, and intellectual disability, a relationship that persisted even among individuals with febrile seizures but not epilepsy.

This month’s Editor’s Choice selection is “Seizures in preterm neonates: A multicenter observational cohort study” by Hannah C. Glass and colleagues. These authors from seven medical centers summarize a prospectively identified cohort of 611 consecutive term and preterm neonates with seizures from their Neonatal Seizure Registry. Subclinical seizures identified by electroencephalography occurred more often in preterm than in term babies, and the mortality rate among the preterm babies was more than twice that in term babies. This collaborative effort provides a wealth of information about a particularly vulnerable population.

  • Seizures in Preterm Neonates: A Multicenter Observational Cohort Study

    Hannah C. Glass, Renée A. Shellhaas, Tammy N. Tsuchida, Taeun Chang, Courtney J. Wusthoff, Catherine J. Chu, M. Roberta Cilio, Sonia L. Bonifacio, Shavonne L. Massey, Nicholas S. Abend, Janet S. Soul On behalf of the Neonatal Seizure Registry study group
    Vol. 72, p19–24

This month’s Editor’s Choice selection is “Pathways for Neuroimaging of Childhood Stroke” by David Mirsky, Lauren Beslow, and other members of the International Pediatric Stroke Study Neuroimaging Consortium and the Pediatric Stroke Neuroimaging Consortium. The advent of non-invasive brain and vascular imaging techniques has greatly facilitated our understanding of cerebrovascular disease in children and allowed us to both confirm the diagnosis of stroke and eliminate other conditions. Imaging techniques evolved rapidly, especially for magnetic resonance imaging, making it more difficult to develop an optimal approach to imaging in children with suspected cerebrovascular dysfunction. This article summarizes the consensus of childhood stroke and imaging experts on the optimal imaging techniques of children with suspected stroke. Such a well-reasoned approach should further increase the value of imaging in the diagnosis and management of stroke in children.

  • Pathways for Neuroimaging of Childhood Stroke

    David M. Mirsky, Lauren A. Beslow, Catherine Amlie-Lefond, Pradeep Krishnan, Suzanne Laughlin, Sarah Lee, Laura Lehman, Mubeen Rafay, Dennis Shaw, Michael J. Rivkin, Max Wintermark for the International Paediatric Stroke Study Neuroimaging Consortium and the Paediatric Stroke Neuroimaging Consortium
    Vol. 69, p11–23

This month’s Editor’s Choice selection is “Optimizing the Diagnosis and Management of Dravet Syndrome: Recommendations From a North American Consensus Panel” by Elaine Wirrell and colleagues. Dravet syndrome is characterized by recurrent convulsions, often triggered by fever, and epileptic encephalopathy in a previously normal child. A mutation of the SCN1A gene encoding a subunit of the neuronal, voltage-gated sodium channel can be identified in at least 85% of individuals with Dravet syndrome. The diagnosis and management of Dravet syndrome provide unique challenges, and Wirrell and colleagues provide much-needed consensus recommendations based upon a systematic literature review.

  • Online Extra
    Optimizing the Diagnosis and Management of Dravet Syndrome: Recommendations From a North American Consensus Panel

    Elaine C. Wirrell, Linda Laux, Elizabeth Donner, Nathalie Jette, Kelly Knupp, Mary Anne Meskis, Ian Miller, Joseph Sullivan, Michelle Welborn, Anne T. Berg
    Vol. 68, p18–34.e3

This month’s Editor’s Choice selection is “Variable White Matter Atrophy and Intellectual Development in a Family With X-linked Creatine Transporter Deficiency Despite Genotypic Homogeneity” by Nicole Heussinger and colleagues. The authors studied a large family with X-linked creatine transporter deficiency due to a confirmed SLC6A8 mutation in an effort to better understand this disorder’s broad phenotypic variability. The most severely affected member of the family exhibited cerebral atrophy and reduced white matter volume compared with control subjects and other family members. Magnetic resonance spectroscopy demonstrated more lower brain creatine levels in hemizygous males than in heterozygous females. The authors suggest that the variability of the disorder’s clinical manifestations may correlate with the extent of the brain creatine depletion and the presence of white matter atrophy.

This month’s Editor’s Choice selection is “Dominant Transmission Observed in Adolescents and Families With Orthostatic Intolerance” by Posey and colleagues. Experienced neurologists are often struck by how often individuals with orthostatic intolerance report family members with similar complaints, and this paper helps to explain this familial tendency. Posey and colleagues analyzed 16 families each with two or more individuals with orthostatic intolerance. The proband of each family underwent heal-up tilt table testing to confirm orthostatic intolerance, and family information was collected using a standardized questionnaire. Pedigree analyses suggested a novel genetic syndrome with a dominant inheritance pattern, incomplete penetrance, and a predominance of symptoms in females. Posey and colleagues provide a basis for additional studies that could identify the genetic mechanisms of orthostatic intolerance and lead to targeted treatments for these individuals.

This month’s Editor’s Choice selection is “Treatment of Neurogenetic Developmental Conditions: From 2016 Into the Future” by van Karnebeek and colleagues. This review offers a fascinating look at the growing number of genetic neurological disorders for which specific treatment strategies have evolved from an increasingly sophisticated understanding of the pathophysiology of these conditions. Effective mechanism-based therapy now exists for some genetic neurological diseases, and we can expect the list of treatment options to grow as research continues.

This month’s Editor’s Choice selection is “Fabry Disease: A Disorder of Childhood Onset” by Raphael Schiffmann and Markus Ries. Fabry disease is an X-linked disorder of glycosphingolipid metabolism that typically presents with an exquisitely painful small fiber neuropathy. Serious later complications include renal failure, stroke, and cardiac dysfunction. Women who carry the mutation often express an array of milder manifestations. Traditional nonspecific treatments for Fabry disease have included the administration of antiepileptic agents to lessen the peripheral nerve pain, medications to control systemic hypertension due to renal disease, and renal transplantation. As outlined by Schiffmann and Ries, the advent of enzyme replacement therapy for Fabry disease has dramatically altered our ability to manage or even prevent the complications of this disorder. Enzyme replacement therapy is expensive and must be life-long, but Fabry disease is one of an increasing number of genetic diseases that can now be effectively treated with gene product replacement, drugs targeting a disorder’s molecular pathways, or gene replacement therapy.

This month’s Editor’s Choice selection is “The Clinical and Electroencephalographic Spectrum of Tilt-Induced Syncope and Near-Syncope in Youth” by Heyer and colleagues. The authors prospectively evaluated 95 children and adolescents with head-upright tilt testing together with video-EEG and continuous blood pressure and heart rate monitoring. They correlated the EEG patterns during the tilt table testing with the occurrence of myoclonus, asystole, vocalizations, and flexion or extension movements. Eighty patients had reflex syncope, and 15 had delayed-onset hypotension without syncope. The duration of EEG slowing with hypotension exceeded the presyncopal interval from onset of slowing to loss of consciousness among the individuals with syncope. Among otherwise healthy individuals in this cohort, orthostatic signs and symptoms varied across the spectrum of tilt-induced reflex syncope and delayed hypotension without syncope. Delayed hypotension without syncope may explain the poorly understood “near syncope” in some individuals.

This month’s Editor’s Choice selection is “Dyscalculia and the Calculating Brain” by Isabelle Rapin. How we learn to use numbers and acquire calculation skills have not been studied as extensively as other aspects of cognition. In recent years, however, functional magnetic resonance imaging and other sophisticated techniques have added greatly to our understanding of these skills. Dr. Rapin is one of the founders of pediatric neurology and has contributed greatly to our understanding of autism, cognitive development, and behavior in children. In this elegant paper Dr. Rapin reviews the recent research on dyscalculia and makes a topic that few of us understand very well seem straightforward.

This month’s Editor’s Choice selection is “Antibody-Mediated Autoimmune Encephalitis in Childhood,” a review by J. Nicholas Brenton and Howard P. Goodkin. Considering how well-recognized autoimmune encephalitis has become, it seems incredible that anti-NMDA antibodies were first documented just less than a decade ago. Progress since then has been dramatic. Several additional autoantibodies have been shown to cause autoimmune encephalitis. Over 400 children and adolescents with autoimmune encephalitis have been documented to date – some 40% of all reported patients. As additional pathologic antibodies are discovered and our experience accumulates, the importance of this condition will continue to grow. Brenton and Goodkin provide a masterful review of the clinical features and pathophysiology of this disorder.

This month’s Editor’s Choice selection is “Pyridoxine-Dependent Epilepsy: An Expanding Clinical Spectrum” by Clara D.M. van Karnebeek and colleagues. Although pyridoxine-dependent seizures was first recognized as a clinical entity in 1954, until recently our understanding of the molecular mechanisms that underlie this dramatic disorder was limited. Here these authors review the genetics and pathophysiology of pyridoxine dependency. By analyzing over 200 reported patients they document a wider phenotypic spectrum than was once suspected.

  • Pyridoxine-Dependent Epilepsy: An Expanding Clinical Spectrum

    Clara D.M. van Karnebeek, Sylvia A. Tiebout, Jikkemien Niermeijer, Bwee Tien Poll-The, Aisha Ghani, Curtis R. Coughlin II, Johan L.K. Van Hove, Jost Wigand Richter, Hans Juergen Christen, Renata Gallagher, Hans Hartmann, Sylvia Stockler-Ipsiroglu
    Vol. 59

Our Editor’s Choice selection is “Pediatric Nerve Biopsy Diagnostic and Treatment Utility in Tertiary Care Referrals” by Ida and colleagues. Precise diagnosis of peripheral nerve disorders promotes more accurate assessment of the prognosis, ensures optimal therapy, and facilitates research. In this paper Ida and colleagues elegantly analyze the peripheral nerve biopsy and genetic testing results of 316 children and adolescents who were evaluated at a tertiary medical center. The nerve biopsy supported a distinct histopathological diagnosis in 106 patients, or about a third of the patients. The biopsy confirmed a suspected diagnosis in 91 children and refined the diagnosis in 182 individuals, or 58%. Importantly, the treatment was modified because of the biopsy results in a quarter of the individuals. These authors demonstrate the continuing usefulness of nerve biopsy even in this age of advanced imaging and molecular testing.

Our Editor’s Choice selection is “Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research” by Comi and colleagues. The recent confirmation that both Sturge-Weber syndrome and isolated pot wine nevi result from a somatic mutation of GNAQ opens the door to new avenues of research that will lead to improved understanding of these disorders and to mechanism-based therapies for some of the serious complications of these conditions. The National Institutes of Health (NIH) sponsored a workshop in 2015 in Bethesda, Maryland that brought together clinical and translational researchers who were asked to identify key knowledge gaps and agree on a research agenda for the next few years. This summary of the group’s ambitious recommendations provides a road-map for research on Sturge-Weber syndrome and port-wine nevi for the next several years.

  • Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research

    Anne M. Comi, Mustafa Sahin, Adrienne Hammill, Emma H. Kaplan, Csaba Juhász, Paula North, Karen L. Ball, Alex V. Levin, Bernard Cohen, Jill Morris, Warren Lo, E. Steve Roach and participants of the 2015 Sturge-Weber Syndrome Research Workshop
    Vol. 58

This month’s Editor’s Choice selection is “Guidelines for Urgent Management of Stroke in Children” by Michael Rivkin and colleagues. This article and two others in this issue grew from an excellent half day symposium at the 2014 Child Neurology Society meeting in Columbus, Ohio. The authors make a compelling argument for the creation of pediatric stroke management centers designed to facilitate the early diagnosis and acute management of stroke in children. Although there are of course important differences between childhood and adult stroke, it is increasingly evident that the rapid diagnosis and treatment provided by an organized pediatric stroke team is likely to yield substantial benefits for many children with stroke.

This month’s Editor’s Choice selection is “The Evaluation and Management of Pediatric Syncope” by Jeffrey B. Anderson and colleagues. Syncope is common among children and adolescents, and it is associated with considerable morbidity. Anderson and colleagues differentiate syncope due to neurological, cardiac and psychogenic origins and provide a clear approach to the diagnosis and management of individuals with syncope. This paper should be a valuable tool for learning about syncope and provide a handy guide for day-to-day patient management.

This month’s Editor’s Choice selection is “Clinical Electroencephalographic Biomarker for Impending Epilepsy in Asymptomatic Tuberous Sclerosis Complex Infants” by Wu and colleagues. Although the majority of children with tuberous sclerosis complex develop epilepsy, the seizures typically begin several months after birth. The onset of poorly controlled seizures, in turn, often heralds the onset of cognitive impairment. This multicenter prospective observational study subjected seizure-free infants with tuberous sclerosis to serial physical examinations and video-EEGs. Three fourths of the patients who developed clinical seizures first developed epileptiform discharges on EEG almost two months before they exhibited clinical seizures. An ability to identify impending seizures in this fashion could provide an opportunity to modify the severity of seizures and cognitive dysfunction.

  • Clinical Electroencephalographic Biomarker for Impending Epilepsy in Asymptomatic Tuberous Sclerosis Complex Infants

    Joyce Y. Wu, Jurriaan M. Peters, Monisha Goyal, Darcy Krueger, Mustafa Sahin, Hope Northrup, Kit Sing Au, Gary Cutter, E. Martina Bebin
    Pediatric Neurology, Vol. 54
    Open Access

This month’s Editor’s Choice selection is “Functional Mapping in Pediatric Epilepsy Surgical Candidates: Functional Magnetic Resonance Imaging Under Sedation With Chloral Hydrate” by Victoria L. Ives-Deliperi and James T. Butler. In selected individuals with intractable epilepsy, surgical ablation of the area of the brain that is responsible for the seizures offers hope for a cure, often after the failure of multiple medications. But whether surgery is feasible hinges strongly on our ability to pinpoint the site where the seizures originate and whether this location overlaps areas that are responsible language and movement. Functional neuro-imaging helps to identify these regions in many patients, but the use of functional imaging is often difficult in small or uncooperative children. Ives-Deliperi and Butler demonstrate that language and motor function can still be assessed with magnetic resonance functional imaging in many children who are tested during sedation. This added bit of information may provide enough pre-operative reassurance to allow some children to undergo potentially curative surgery.

This month’s Editor’s Choice selection is “Glucose Transporter Type I Deficiency (G1D) at 25 (1990-2015): Presumptions, Facts, and the Lives of Persons With This Rare Disease.” Although glucose transporter deficiency is rare, its recognition is important because it is at least partially treatable. Juan M. Pascual and Gabriel M. Ronen review this disorder from a patient and historical perspective 25 years after it was first described, pointing out assumptions and preconceived notions that are not experimentally supported or that are directly contradicted by the evidence.

This month’s Editor’s Choice selection is “Clinical Use of Cerebrospinal Fluid Neurotransmitters” by Rodan and colleagues. Analysis of cerebrospinal fluid (CSF) neurotransmitters allows us to confirm a variety of neurological disorders that would otherwise remain unexplained. Importantly, several of the disorders diagnosed by CSF neurotransmitter analysis respond dramatically to targeted therapy, so the ability to identify these conditions is practically important. Rodan and colleagues’ flawless summary of the conditions that can be confirmed with CSF neurotransmitter analysis should be must reading for child neurologists and other physicians who see children with neurological disease.

This month’s Editor’s Choice selection is “Randomized, single-blind, parallel clinical trial on the efficacy of oral prednisolone versus intramuscular corticotropin on immediate and continued spasm control in West syndrome” by Wanigasinghe and colleagues. The optimal treatment for infantile spasms has been controversial for decades, and, with few well-designed, adequately powered clinical trials to guide therapy, the arguments have often shed more heat than light. In what may become a landmark paper, Wanigasinghe and associates present the results of a large, randomized trial pitting intramuscular synthetic ACTH against oral prednisolone in children with infantile spasms (see also the editorial by Mytinger and Camfield). Given the extraordinary cost and difficulty of administration of ACTH, its lack of superiority over prednisolone is an important finding. Some will criticize the study’s low ACTH dose, which was based on the United Kingdom Infantile Spasms Study protocol, or carp about the use of synthetic ACTH, and future trials may address these issues. But for now this trial should make even the most ardent ACTH disciples pause and reassess.

  • Randomized, Single-Blind, Parallel Clinical Trial on Efficacy of Oral Prednisolone Versus Intramuscular Corticotropin on Immediate and Continued Spasm Control in West Syndrome

    Jithangi Wanigasinghe, Carukshi Arambepola, Shalini Sri Ranganathan, Samanmalie Sumanasena, Gangani Attanapola
    Pediatric Neurology, Vol. 53, Issue 3

This month’s Editor’s Choice selection is “The diagnosis and management of concussion in children and adolescents” by Rose and colleagues. Concussion has received increasing attention in recent years, both from the physicians charged with treating these patients and from the legislative leaders who have enacted more stringent rules governing continued participation in sports activities following a suspected concussion. Because of more precise definitions of concussion and increased awareness on the part of physicians, parents, and coaches, the number of children and adolescents diagnosed with concussion has increased sharply in recent years. Rose and colleagues provide a thorough review of the epidemiology, pathophysiology, diagnosis, and therapy of concussion in children and adolescents. The paper will be of great help to anyone who cares for head injured children and those engaged in research on traumatic brain injury.

This month’s Editor’s Choice selection is “Virus and Immune-Mediated Encephalitides: Epidemiology, Diagnosis, Treatment, and Prevention” by James F. Bale. Although encephalitis is a well-known clinical entity, our understanding of its causes and pathophysiology continues to evolve. Subacute sclerosing panencephalitis and varicella-zoster virus-associated conditions have largely disappeared in developed countries due to widespread vaccinations but persist in other regions. In contrast, West Nile virus, non-polio enterovirus encephalitis, and immune-mediated encephalitis are increasingly recognized. Bale provides a thorough analysis of these and other developments that clinicians will find extremely useful.

This month’s Editor’s Choice selection is “Acute Pediatric Encephalitis Neuroimaging: Single-Institution Series as Part of the California Encephalitis Project” by Bykowski and colleagues. The diagnosis of encephalitis in children can be challenging because of the clinical manifestations and cerebrospinal fluid findings vary and the neuroimaging findings are often nonspecific. These authors analyzed the imaging findings of 141 children with clinically suspected encephalitis. Acutely, 23% (22/94) of the children had abnormal findings on computed tomography, while 50% (67/134) of the children exhibited abnormalities on magnetic resonance imaging. Although patients with complex magnetic resonance imaging abnormalities tended to have more severe disease manifestations and a longer hospital stay, the imaging findings were nonspecific and none of the findings correlated with a specific pathogen. Nevertheless, this careful analysis of such a large cohort provides a wealth of information about the imaging features of these children.

This month's Editor's Choice selection is "Thyroid-Related Neurological Disorders and Complications in Children" by Debika Nandi-Munshi and Craig E. Taplin. Thyroid hormones play a vital role in mammalian metabolism, and hypothyroidism results in cognitive dysfunction, peripheral neuropathy, and myopathy. Thyroid hormone is even more critical to the developing brain, which will be irreparably harmed by inadequate thyroid stores. Hashimoto's thyroiditis is often associated with immune-mediated brain dysfunction, and hyperthyroidism can result in anxiety, tremor, and myopathy. Nandi-Munshi and Taplin provide a superb review of the pathophysiology of thyroid-related neurological disease as well as a wealth of practical information about its diagnosis and management. Every neurologist will find this paper useful, and for this reason, it is the Editor's Choice selection.

Focal hyperintensities on T2-weighted MRI were first recognized in individuals with NF1 soon after the advent of MRI, but the nature of these sometimes fluctuating lesions is still debated. In this month’s Editor’s Choice selection, Pondé Rodrigues and colleagues studied 42 individuals with NF1 and 25 controls with MRI spectroscopy of a predetermined region of the basal ganglia, where the signal hyperintensities of NF1 are most likely to occur. The preservation of NAA values even in individuals with characteristic basal ganglia lesions suggests neuronal stability within the area, which favors the notion that the lesions represent intramyelinic edema instead of focal demyelination and axonal degeneration.

  • Is Magnetic Resonance Spectroscopy Capable of Detecting Metabolic Abnormalities in Neurofibromatosis Type 1 That Are Not Revealed in Brain Parenchyma of Normal Appearance?

    Antonio Carlos Pondé Rodrigues Jr., José Roberto Lopes Ferraz-Filho, Ulysses S. Torres, Antônio José da Rocha, Marcos Pontes Muniz, Antônio Soares Souza, Eny Maria Goloni-Bertollo, Érika Cristina Pavarino
    Vol. 52, Issue 3, p314–319

This month’s Editor’s Choice selection is “Tremor in a Population-Based Cohort of Children in New York City” by Elan D. Louis and colleagues. Their systematic study of 317 children provides much needed information about the incidence, clinical features, and associated findings of tremor among children. Mild tremor was surprisingly common (33.1%) in this cohort, but more noticeable tremor occurred in 2.2% of the children. Tremor was more often apparent in the non-dominant hand. The most frequent comorbidities were medication utilization for conditions such as attention deficit disorder, depression, or epilepsy.

Although many individuals with tuberous sclerosis complex do not have severe intellectual disability, experienced clinicians have long recognized that these many of these patients exhibit an array of more subtle cognitive changes that present in a variety of ways. In this month’s Editor’s Choice selection, de Vries and colleagues present a new checklist designed to promote early recognition of cognitive and behavioral dysfunction in individuals with tuberous sclerosis complex. The tuberous sclerosis associated neuropsychiatric disorders (TAND) Checklist provides the clinicians caring for tuberous sclerosis patients with an easily administered tool that should facilitate the early identification and treatment of these individuals.

Current guidelines suggest routine cranial ultrasound screening for all babies born before 30 weeks’ gestation. Although it is generally accepted that brain lesions are more common in increasingly premature babies, we have had little information about the frequency of brain lesions in babies who are less premature. Ballardini and colleagues extended universal cranial ultrasound screening to their moderately premature patients, and here they analyze the cranial ultrasound results of 724 consecutive babies of 33-36 week gestation. The frequency of intracranial lesions was inversely proportional to the gestational age, ranging from 3.7% in the 36 week neonates to 27.1% at 33 weeks of gestation. The abnormality rate increased in association with the need for respiratory support, a low 5 minute Apgar, and other factors. These methodically collected data fill a large gap in our knowledge. The authors propose that moderately premature babies should undergo cranial ultrasonography, particularly in the presence of risk factors that increase the likelihood of brain lesions.

  • Universal Cranial Ultrasound Screening in Preterm Infants With Gestational Age 33-36 Weeks. A Retrospective Analysis of 724 Newborns

    Elisa Ballardini, Anna Tarocco, Alessandro Baldan, Elisa Antoniazzi, Giampaolo Garani, Caterina Borgna-Pignatti
    Vol. 51, Issue 6, p790–794

On April 15, 2013, three people were killed and 264 others were injured when two bombs were detonated near the finish line of the Boston Marathon. The days that followed played out on the world stage via relentless media coverage. The people of Boston were told to shelter in place, business were closed, armored vehicles patrolled the city’s streets, and the perpetrators of the bombing were killed or apprehended. What effect does such a shared trauma have on the people of a city and, especially on the children of a city? Many of us can remember major traumatic episodes from childhood vividly, even after half a century, so the effect is both profound and lasting. In this month’s Editor’ Choice article, Guerriero and colleagues document a three-fold increase in the number of children and adolescents presenting to their emergency department with a functional neurological complaint following the bombing. Almost three-fourths of these individuals reported some type of prior psychiatric diagnosis, and most of those affected presented week or more after the bombing. Shared traumas such as this take a toll on children, and patients with pre-existing psychological dysfunction seem to be particularly vulnerable.

  • Increased Pediatric Functional Neurological Symptom Disorders After the Boston Marathon Bombings: A Case Series

    Réjean M. Guerriero, Danielle B. Pier, Claudio M. de Gusmão, Miya E. Bernson-Leung, Kiran P. Maski, David K. Urion, Jeff L. Waugh
    Vol. 51, Issue 5, p619–623

This month’s Editor’s Choice selection is “Cognitive phenotype in ataxia-telangiectasia” by Franziska Hoche and colleagues. Homer Smith once remarked “Though we name the things we know, we do not necessarily know them because we name them.” And so it is with ataxia-telangiectasia, whose name derives from its two most prominent and consistent early clinical features. But the phenotype of ataxia-telangiectasia is much less simplistic than its name might suggest. In a study of 22 individuals with ataxia-telangiectasia in this issue of Pediatric Neurology, Hoche and colleagues demonstrate significant cognitive impairment even among individuals with early stage cerebellar dysfunction. Those with more severe cerebellar dysfunction had more severe cognitive impairment. Whether cognition is affected by the degeneration of the subcortical structures or directly by the gene dysfunction itself may require additional study, but delineation of the cognitive deficits and their progressive nature represents a major step forward in our understanding of this ataxia-telangiectasia.

Hypersensitivity reactions are common with antiepileptic medications, and the offending drug is typically discontinued when the nature of the difficulty is recognized. Cessation of a given medicine is not problematic as long as another equally-effective and better tolerated agent is available. But an allergic reaction triggered by an effective drug represents a major setback when the other medications are ineffective or not tolerated. This month’s Editor’s Choice selection is “HLA genotypes and trial of desensitization in patients with oxcarbazepine-induced skin rash” by Lee and colleagues. They slowly reintroduced oxcarbazepine to 19 individuals who had experienced an excellent clinical response but then developed an allergic reaction. By reintroducing oxcarbazepine at 0.1 mg per day and gradually titrating the dose over several months, the authors were able to reinstate oxcarbazepine in 18 of 19 patients. This approach should be a feasible way to restart medications as well. Given the length of time needed to titrate the drug, most clinicians faced with a medicine allergy will opt to simply switch to another drug. But for the individuals who have responded beautifully to one drug only to develop an allergic reaction, this desensitization approach may allow some patients to continue taking the most effective medication.

This month’s Editor’s Choice article is “The efficacy of moderate-to-high dose oral prednisolone versus low-to-moderate dose intramuscular corticotropin for improvement of hypsarrhythmia in West syndrome: A randomized, single-blind, parallel clinical trial” by Wanigasinghe and colleagues. The optimal treatment of infantile spasms has been a controversial topic for years, and there has been no shortage of debate. What has often been in short supply, however, is good evidence to support the sometimes contentious debate about whether individuals with infantile spasms should receive ACTH or corticosteroids. This report by Wanigasinghe and colleagues will not stop the debate, because it focuses on the EEG response, not the patient outcome. But a large number of patients enrolled in a randomized trial cannot be easily dismissed, because the electrographic response in these patients often mirrors the clinical response. Other reports from this trial may finally settle this debate.

  • The Efficacy of Moderate-to-High Dose Oral Prednisolone Versus Low-to-Moderate Dose Intramuscular Corticotropin for Improvement of Hypsarrhythmia in West Syndrome: A Randomized, Single-Blind, Parallel Clinical Trial

    Jithangi Wanigasinghe, Carukshi Arambepola, Shalini Sri Ranganathan, Samanmali Sumanasena, Eindrini C. Muhandiram
    Vol. 51, Issue 1, p24–30

This month’s Editor’s Choice selection is “Rise in Late Onset Vitamin K Deficiency Bleeding in Young Infants Because of Omission or Refusal of Prophylaxis at Birth” by Schulte and colleagues. In an accompanying editorial, Joseph Volpe notes that the routine administration of vitamin K to newborns has all but eliminated hemorrhagic disease of the newborn in most developed countries. The authors document that parents refused vitamin K administration for 28% of the babies born in nearby community birthing centers and 3.4% of those born in their own academic medical center. Seven babies developed severe vitamin K-dependent coagulopathy, and complications included intracranial or gastrointestinal hemorrhage. This this article provides a sobering reminder of what can occur in newborns who do not receive vitamin K.

Despite the recent attention given to concussion and post-concussion syndrome in children and adolescents, management decisions for these individuals must often be made without objective evidence. Chronic headache following a concussion is a particularly difficult clinical problem. This month’s Editor’s Choice article is “Does Analgesic Overuse Contribute to Chronic Post-traumatic Headaches in Adolescent Concussion Patients?” by Heyer and Idris. They demonstrate that most of the adolescents with chronic headache after a concussion consume too many analgesics, and, more importantly, that the headaches resolve or return to baseline severity in many of those who cease the medication overuse. This is precisely the kind of practical information that we need to guide therapy for these patients.

This month’s editor’s choice selection is “Surgical Treatment of Subependymal Giant Cell Astrocytoma in Tuberous Sclerosis Complex Patients” by Kotulska and colleagues. Summarizing 64 subependymal giant cell astrocytoma surgeries in 57 tuberous sclerosis complex patients with at least 12 months of follow-up, this is the largest and most carefully studied series yet to appear in the literature. Recent attention has focused on the use of mTOR inhibitors for giant cell tumors, but surgery is likely to remain the optimal treatment for some individuals. This paper contains a wealth of information about the clinical manifestations, treatment, and outcome of these individuals.

  • Surgical Treatment of Subependymal Giant Cell Astrocytoma in Tuberous Sclerosis Complex Patients

    Katarzyna Kotulska, Julita Borkowska, Marcin Roszkowski, Marek Mandera, Paweł Daszkiewicz, Krzysztof Drabik, Elzbieta Jurkiewicz, Magdalena Larysz-Brysz, Katarzyna Nowak, Wiesława Grajkowska, Dorota Domańska-Pakieła, Sergiusz Jóźwiak
    Vol. 50, Issue 4, p307–312

A patent foramen ovale (PFO) is a common but usually harmless anomaly, but it facilitate stroke due to paradoxical embolism and may be linked to migraine with aura. Whether to close a PFO in stroke patients has long been a point of controversy, particularly since the development of percutaneous closure devices have made closure easier. But recently completed randomized clinical trials in adult stroke patients failed to demonstrate a lower secondary stroke risk following PFO closure. The data pertaining to PFO closure in children are not as robust, but such large scale trials would be impossible to do in children and there is little reason to believe the results would differ.

This month’s Editor’s Choice is Menon and colleagues’ analysis of 153 individuals less than age 20 years who underwent percutaneous closure of a PFO because of migraine, transient ischemic attacks, or stroke-like symptoms. Some of the patients subjectively improved despite residual intracardiac shunts, and the inclusion of more than one diagnosis makes the results more difficult to interpret. Nevertheless, this paper contains a wealth of information that is particularly timely.

This month’s Editor’s Choice article is “Hippocampal Volumes in Juvenile Neuronal Ceroid Lipofuscinosis: A Longitudinal Magnetic Resonance Imaging Study” by Tokola and colleagues. Juvenile neuronal ceroid lipofuscinosis is a heterogeneous genetic disorder that leads to progressive visual loss, severe epilepsy, and steady deterioration of motor function and cognition. Cerebral and cerebellar atrophy are well documented, but Tokola and associates studied the hippocampal volume over a five year interval in eight patients and ten age and gender matched controls. The 3.3% annual hippocampal volume loss exceeds the previously documented annual 2.4% loss of total gray matter volume in this condition.

This month’s Editor’s Choice selection is “The Ketogenic Diet: Initiation at Goal Calories Versus Gradual Caloric Advancement” by Bansal and colleagues. It has been almost a century since Keith and Helmholtz described the use of a high fat, low carbohydrate diet as a treatment for epilepsy, so potential improvements in the way we administer the diet are surprising. In many centers the ketogenic diet is initiated with fasting followed by a gradual introduction of the desired fat to carbohydrate calorie ratio. Bansal and colleagues show that moving directly to the target caloric ratio is simpler, well-tolerated, and ultimately more effective than the traditional approach.

This month's Editor's Choice selection is "Automatically Quantified Diffuse Excessive High Signal Intensity on MRI Predicts Cognitive Development in Preterm Infants” by Parikh and colleagues. Experienced child neurologists are well-aware of how difficult it is to predict cognitive outcome in preterm babies. In the absence of striking abnormalities, neither the bedside examination nor currently available diagnostic modalities seem to be of much use in establishing the prognosis. Although the work is preliminary, Parikh and colleagues correlated cognitive and language impairment with objective, automatically quantified white matter changes on MRI. This approach could provide a much-needed way to establish a more accurate prognosis for these babies.

  • Automatically Quantified Diffuse Excessive High Signal Intensity on MRI Predicts Cognitive Development in Preterm Infants

    Nehal A. Parikh, Lili He, Eliana Bonfante-Mejia, Leo Hochhauser, Patricia Evans Wilder, Katrina Burson, Supreet Kaur
    Vol. 49, Issue 6, p424–430

This month’s Editor’s Choice selection is “Pediatric Idiopathic Intracranial Hypertension: A Need for Clarification.” In this essay, Aylward proposes new diagnostic criteria for idiopathic intracranial hypertension in children. He also suggests new nomenclature that eloquently solves many of the age-old terminology problems with this condition.

This month’s Editor’s Choice paper is “Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus” by Northrup and colleagues. Creating diagnostic criteria for tuberous sclerosis complex is particularly challenging because of its numerous and diverse clinical signs, its striking phenotypic variability, and the age-related nature of some lesions. These revised diagnostic criteria benefit from years of accumulated knowledge about the clinical features of tuberous sclerosis complex and from an increasingly sophisticated understanding of its molecular biology. The new criteria are also simpler to use than previous versions and should be a useful clinical tool for many years.

  • Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference

    Hope Northrup, Darcy A. Krueger on behalf of the International Tuberous Sclerosis Complex Consensus Group
    Vol. 49, Issue 4, p243–254
    Open Access

The Editor’s Choice selection this month is “National Variation in Costs and Mortality for Leukodystrophy Patients in US Children’s Hospitals” by Brimley and colleagues. More precise outcome and cost data have become increasingly important we struggle contain costs and establish a rational health care policy. Some of these facts can be gleaned from existing administrative databases that contain a wealth of information about costs, regional differences, and outcome. Brimley and colleagues utilized the Pediatric Health Information System, a network of 43 American children’s hospitals, to examine health care costs and mortality for children with leukodystrophy. The information in these databases may be less exact than that of a prospective disease registry, but the information is already compiled and is often useful. The utility of administrative databases in the study of rare diseases is well-illustrated by this article on leukodystrophy, which documents the substantial cost of caring for children with leukodystrophy as well as the variability in care that exists in different regions.