Tag Archive for: Berl

A blue background showcases a brain made of gears, symbolizing the intricate workings of the mind.A blue background showcases a brain made of gears, symbolizing the intricate workings of the mind.

Measuring preschoolers’ cognitive development in Latin America

A blue background showcases a brain made of gears, symbolizing the intricate workings of the mind.A blue background showcases a brain made of gears, symbolizing the intricate workings of the mind.

Neurodevelopment occurs at a rapid pace during the preschool years, research shows.

Measuring and tracking development in early childhood is important for understanding how to best support long-term positive health outcomes for children. However, the art of selecting measurement tools that are appropriate for a given study sample is complex; variations in language, cultural relevance and adaptations, availability of normative data, and more can impact the administration and interpretation of study findings.

In a recent study published in the Journal of Pediatric Psychology, the authors systematically review the standardized neurodevelopmental assessments used to study preschool-aged children’s cognitive development in Spanish-speaking Latin America.

“Thinking critically about the ways we measure these outcomes is an important first step in conducting ethical and accurate global research,” said Meagan Williams, M.S.P.H., C.C.R.C., senior clinical research coordinator for the division of Infectious Diseases and the Zickler Family Prenatal Pediatrics Institute at Children’s National Hospital and corresponding author of the study.

The hold-up in the field

The field of child development research is complicated by the presence and use of many different neurodevelopmental assessment tools, only some of which are standardized and use norms to allow researchers to compare their cohorts’ performance with population-level data.

“Many cognitive assessments, including some of the most commonly used assessments identified in our review of research conducted in Spanish-speaking Latin America, have only been officially normed in the United States,” Williams added. “Others have been translated into Spanish and normed in large countries such as Mexico or Spain, but Latin America is a large and culturally diverse region, and it is unclear whether these normative samples are generalizable and culturally relevant to other regions of Spanish-speaking Latin America.”

This systematic review outlined 41 different neurodevelopmental assessments used in 97 studies, including information about each study’s sample, use of each measurement tool and findings related to child cognitive development. The review goes into detail about the most widely used assessments, including background information of each assessment and trends in how authors of the studies in this review reported their methods and results.

Moving the field forward

When researchers use similar methods and valid outcome measures across studies, it becomes possible to combine data between cohorts and draw stronger conclusions about child outcomes. For example, The Wechsler Preschool and Primary Scale of Intelligence (WPPSI) was identified as the most used tool to measure intelligence of young children ages 2-6 in the systematic review. The WPPSI is also one of many assessments that Williams’s research team, led by Sarah Mulkey, M.D., is using to measure neurodevelopment among children exposed to Zika virus in utero.

“If researchers studying longitudinal outcomes after Zika virus exposure also use the WPPSI for their study samples – and if they openly report on their methods, adaptations, and sample characteristics – then it may be possible to harmonize data from multiple cohorts and draw stronger conclusions across studies,” Williams said.

But even the most popular and widespread assessments such as the WPPSI are not without their limitations. While norms exist for regions such as the United States and Mexico, additional work needs to be done to appropriately adapt and validate these tools for use in other populations.

Benefiting patients

Neurodevelopment occurs at a rapid pace during the preschool years. The earlier neurodevelopmental delays can be identified, the earlier experts can administer interventions to respond to these delays and help children get back on track with their peers.

This is particularly salient for research conducted in low- and middle-income countries, where socioeconomic, environmental and other exposures that are known to impact child development differ from those in higher-resource settings. Internationally, there appears to be significant variability in not only the assessment tools which are selected for use, but also in the methods reported across studies to conduct and interpret these assessments.

“By coming together as a field and prioritizing the use and validation of common and culturally appropriate assessments, we can better understand child outcome data on both an individual study level as well as on a broader population level, which will lead to a better understanding of the unique needs and strengths of the children we serve,” Williams said.

The team at Children’s National has been studying the neurodevelopment of children exposed to the Zika virus in Colombia since the beginning of the Zika epidemic.

“As our study on Zika virus has overlapped with the COVID-19 pandemic, we have had the opportunity to collect child outcome data at a very interesting time in history. We are excited that this review revealed that we chose a popular and well-studied assessment for our data collection in this region and we look forward to publishing our 5-year outcome data (which will include WPPSI data) in the coming year,” Williams and Mulkey concluded.

Dr. Mulkey is committed to studying the long-term neurodevelopmental impacts that viruses like Zika and SARS-CoV-2 have on infants born to mothers who were infected during pregnancy through research with the Congenital Infection Program at Children’s National and in collaboration with colleagues in Colombia.

Additional Children’s National authors include Madison Berl, Ph.D.

illustration of neurons with electrical impulses

Children’s National at the American Epilepsy Society Annual Meeting

illustration of neurons with electrical impulsesSeveral experts from Children’s National Hospital will be sharing their knowledge at the upcoming American Epilepsy Society Annual Meeting in Orlando, December 1-5. Here’s a sample of what you can expect.

  • Chima Oluigbo, M.D., a pediatric neurosurgeon, will be on panel with other surgeons discussing different surgical techniques and approaches related to epilepsy surgery followed by hands-on practice at teaching stations. He will focus on extra-temporal epilepsy scenarios and will be presenting on Nuances of Temporal Lobe Surgery in the Pediatric Population at the Neurosurgery Symposium highlighting Surgical Controversies in Temporal Lobe Epilepsies.
  • Ersida Buraniqi, M.D., a child neurologist, will be part of a special interest group on critical care and discuss advances in electroencephalography (EEG) and multimodal neuro-monitoring for seizures in the intensive care unit (ICU). Dr. Buranigui will be doing a special presentation on EEG features to predict electrographic seizures and mortality in the pediatric intensive care unit (PICU).
  • Dana Harrar, M.D., director of Pediatric Stroke Program and co-director of Critical Care Neurology, is presenting at an invitation-only resident EEG course, providing an interactive structured curriculum on pediatric and adult EEG. Dr. Harrar will be focusing on doing an ICU-EEG nomenclature overview.
  • Madison Berl, Ph.D., director of Neuropathy Research and of the Intellectual and Developmental Disabilities Research Center Program, will be presenting during the AES Annual Course. The topic “It’s About Time” will focus on the critical importance the timing in epilepsy care plays in patient outcome. Dr. Berl will be presenting on neuropsych outcomes.
  • Leigh Sepeta, Ph.D., director of Inpatient Neuropsychology, is the vice-chair of the special interest group on neuropsychology. Additionally, Freya Prentice, M.Sc., will be doing a presentation during this session on functional mapping of the cognitive memory circuit in pediatric epilepsy.
Date Time Presenter(s) Title
12/2/23 8:00 am Chima Oluigbo, M.D., FRCSC, FAANS Skills Workshop | Epilepsy Surgery Workshop: Techniques and Clinical Scenarios
12/2/23 5:30 pm Chima Oluigbo, M.D., FRCSC, FAANS SIG | Epilepsy Surgery: Homunculus Revisited: Managing Central Lobe Epilepsies
12/2/23 5:30 pm Ersida Buraniqi, M.D. SIG | Critical Care: Advances in EEG and Multimodal Neuro-monitoring for Seizures in the ICU
12/2/23 7:00am Dana Harrar M.D. Resident EEG Course
12/3/23 9:00 am Chima Oluigbo, M.D., FRCSC, FAANS Neurosurgery Symposium | Surgical Controversies in Temporal Lobe Epilepsies
12/3/23 8:45 am Madison Berl, Ph.D. Annual Course | It’s About Time: Timing in Epilepsy Evaluation and Treatment
12/4/23 7:00 am Leigh Sepeta, M.D. SIG | Neuropsychology: Mapping Cognition in Epilepsy: From the Lab to the Clinic
12/4/23 7:00 am Freya Prentice, M.D. SIG | Neuropsychology: Mapping Cognition in Epilepsy: From the Lab to the Clinic
12/5/23 7:00 am Dana Harrar M.D. SIG | Epilepsy Education: Epilepsy Education Throughout the Training Pipeline

 

MRI of the patient's head close-up

Madison Berl, Ph.D., receives 2020 PERF award for Infrastructure/Registry Research

MRI of the patient's head close-up

The Pediatric Epilepsy Research Foundation Grant (PERF) has awarded Madison Berl, Ph.D., neuropsychologist at Children’s National Hospital, the 2020 PERF award for Infrastructure/Registry Research. The funds will support her work on researching neuropsychological outcomes of children being considered for pediatric epilepsy surgery.

This grant, which provides $200,000 of research funding, will allow Dr. Berl to systematically collect data outcomes and create robust prediction models that are critical to achieving precision medicine that allows for selecting the most effective surgical treatment for an individual child.

“While seizures are a critical outcome, there is increasing recognition that outcomes beyond seizure control is critical to children and their families when evaluating and treating the impact of epilepsy and its treatments,” said Dr. Berl.

Guidelines and consensus statements related to pediatric epilepsy surgery are uniformly lacking high quality published outcome data to support clinical decisions that impact likelihood of seizure freedom and optimizing outcomes beyond seizures (e.g., neuropsychological functioning, quality of life, improved sleep). Despite recognition of the need for standardized collection of data on a multi-institutional basis, the efforts that exist are limited in scope.

Moreover, as new techniques – such as laser ablation and brain stimulation – are approved for pediatric patients, there is little information available to determine which children will benefit from which intervention.

“This project fundamentally is a multi-site registry for epilepsy surgery outcomes,” Dr. Berl added.

“However, this type of infrastructure also fosters growth and active collaboration within a network of pediatric epilepsy clinicians. I am excited because if successful, this will be the start of long-term collaborative effort.”

William Gaillard

Putting childhood epilepsy in the spotlight at American Epilepsy Society Meeting

William Gaillard

“We aim to build the evidence base for treatments that are effective specifically for children with epilepsy,” says William D. Gaillard, M.D., chief of Child Neurology, Epilepsy and Neurophysiology, and director of the Comprehensive Pediatric Epilepsy Program.

While epilepsy affects people of all ages, the unique way it manifests in infants, children and adolescents can be attributed in part to the complexities of the growing and developing brain. Researchers from the Children’s National Comprehensive Pediatric Epilepsy Program brought their expertise on the challenges of understanding and treating epilepsy in children to the recent American Epilepsy Society Annual Meeting, the largest professional gathering on epilepsy in the world.

“We aim to build the evidence base for treatments that are effective specifically for children with epilepsy,” says William D. Gaillard, M.D., chief of Child Neurology, Epilepsy and Neurophysiology, and director of the Comprehensive Pediatric Epilepsy Program. “We have learned much from studies in adult populations but technologies like functional MRI allow us to get in-depth understanding, often in non-invasive ways, of precisely how epilepsy is impacting a child.”

Dr. Gaillard was also recently elected to serve as the Second Vice President of the American Epilepsy Society. “The AES is the largest multidisciplinary professional and scientific society dedicated to the understanding, treatment and eradication of epilepsy and associated disorders, and I am honored to serve as the new Second Vice President,” he said.

The team’s presentations and poster sessions focused on several key areas in pediatric epilepsy:

Better ways to see, measure and quantify activity and changes in the brain for children with epilepsy before, during and after surgery

  • Novel applications of fMRI for children with epilepsy
    • Evaluation of an fMRI tool that tracks verbal and visual memory in children with epilepsy – one of the first to capture memory functions in this population of children using noninvasive fMRI;
    • Early study of the use of “resting-state” fMRI to map language skills before epilepsy surgery – an important first step toward noninvasively evaluating children who are too young or neurologically impaired to follow tasks in traditional MRI studies;
  • A study of whether intraoperative MRI, i.e. imaging during neurosurgery, allows for more complete removal of abnormal brain tissue associated with focal cortical dysplasia in children, which is a common cause of intractable epilepsy;
  • A preliminary case review of existing data to see if arterial spin labeling MRI, which measures blood flow to the brain, has potential to identify blood flow changes in specific locations of the brain where seizures occur;
  • An analysis of language laterality – the dominant side of the brain controlling language –  questioning the true reasons that the brains of children with epilepsy have differences in the hemisphere that predominantly controls language;
  • A review of some common assessments of language and working memory that are used pre- and post-operatively to gauge the impacts of pediatric epilepsy surgery. The study found that using multiple assessments, and studying results individually rather than as a group average, resulted in a more complete picture of the outcomes of surgery on these areas of brain function;
  • A preliminary study examining whether continuous EEG monitoring of neonates with hypoxic ischemic encephalopathy, or lack of oxygen to the brain, can be a reliable predictor of neurodevelopmental outcomes while the infant is undergoing therapeutic hypothermia.

“In order to expand our understanding of causes, impacts and outcomes, the range of research is broad given the complexity of epilepsy,” says Madison M. Berl, Ph.D. “This is the only way we can contribute to the goal of providing our colleagues and the families they serve with better resources to make informed decisions about how best to assess and treat pediatric epilepsy.”

The molecular, genetic and biological factors that contribute to onset and severity of pediatric epilepsy

  • A retrospective study of young patients with malformations in cortical development that are important causes of childhood epilepsy;
  • Investigation of a simple saliva test to effectively identify the presence of two common viral infections, human herpesvirus-6B and Epstein-Barr virus, that may be contributors to onset of epilepsy in otherwise normally functioning brains;
  • A preliminary review of the possible relationship between febrile infection-related epilepsy syndrome and the co-occurrence of another neuro-inflammatory condition – hemophagocytic lymphohistiocytosis.

Madison Berl, Ph.D., director of research in the Division of Pediatric Neuropsychology, and a pediatric neuropsychologist in the Comprehensive Pediatric Epilepsy Program, adds, “In order to expand our understanding of causes, impacts and outcomes, the range of research is broad given the complexity of epilepsy. This is the only way we can contribute to the goal of providing our colleagues and the families they serve with better resources to make informed decisions about how best to assess and treat pediatric epilepsy.”

Expanding awareness of SUDEP

Madison Berl

Madison M. Berl, Ph.D., is helping to expand awareness of SUDEP among patients, families and caregivers.

When 4-year-old Henry Lapham died in his sleep just weeks after being diagnosed with epilepsy in 2009, it was a shock to everyone — even his pediatrician and neurologist. Henry’s cause of death was sudden unexpected (or unexplained) death in epilepsy persons (SUDEP), a condition that causes sudden death in about 1 of every 1,000 otherwise healthy patients with epilepsy. Neither health care professional had mentioned this as a possibility, as remote as it was.

“I was desperate to make sense out of our tragedy,” writes Henry’s mother, Gardiner Lapham, R.N., M.P.H., in “Increasing awareness of sudden death in pediatric epilepsy together,” an article published in the February 2017 issue of Pediatrics. After her son’s death, by working with a group called Citizens United for Epilepsy Research, Lapham connected with other families affected by the same heartbreak. “I have met many bereaved family members,” she adds, “and the most consistent thing I hear is that they wish they had known about SUDEP.”

Now, a new collaboration with Children’s National Health System, where Henry received care, University of Virginia Medical Center (UVA) and other academic medical centers is helping to expand awareness of SUDEP among patients, families and caregivers alike. Known as Childhood Epilepsy Risks and Impact on Outcomes (CHERIO), the multiyear effort aims to develop approaches to increase knowledge about SUDEP and other conditions that can accompany epilepsy, such as attention deficit hyperactivity disorder, autism, anxiety, depression and sleep issues, according to co-authors of the Pediatrics article.

CHERIO got its start in 2014 at the American Epilepsy Society annual meeting. There, Lapham met Madison M. Berl, Ph.D., director of research, Division of Pediatric Neuropsychology at Children’s National, who studies epilepsy comorbidities. When Lapham asked what she could do to help raise awareness of SUDEP at Children’s National, she and Berl, along with William Davis Gaillard, M.D., Henry’s neurologist, hatched a plan.

Working with multiple disciplines and stakeholders, including neuropsychologists, psychiatrists, neurologists, epidemiologists, basic scientists, nurses and parent advocates at both Children’s National and UVA, CHERIO plans to assess the level of knowledge about SUDEP and other epilepsy comorbidities among medical providers and parents and to implement ways to increase knowledge. The first item on the agenda, Berl explains, was to conduct a survey to see just how much doctors knew about SUDEP.

“Although many neurologists are aware of this condition, ours was the first to survey pediatricians, and the majority was not aware of SUDEP – despite having children with epilepsy in their practice,” Dr. Gaillard says. “We know that many neurologists do not discuss SUDEP with patients and the reasons for not talking about SUDEP are varied. Thus, CHERIO felt that in addition to educating neurologists about the need to discuss the risk of death associated with epilepsy, increasing pediatricians’ awareness of SUDEP is one approach that could open more opportunities for families to have this discussion.”

To help make it easier to talk about this risk, the CHERIO team is developing strategies for doctors to start the conversation with patients and their families by framing SUDEP in the context of more common epilepsy comorbidities.

“Clinicians walk a fine line in giving information at the right time to make people more aware,” Berl adds, “but also being realistic and giving information that fits with what’s going on in a particular child’s case. By discussing SUDEP along with other, more common epilepsy risks, it brings context to a family so that they’re not unduly concerned about death – which also can paralyze a family and create unnecessary alarm.” The risk of death in most children with epilepsy is very low, slightly higher than the risks faced by healthy children. But parents of children with complicated epilepsy who have more risk factors for sudden death should be especially aware , she says.

Another way to help facilitate discussion may be through a simple tweak in the medical record, Berl adds. The team is currently developing a checklist that pops up annually in a patient’s medical record to remind clinicians of important points to discuss with patients and their families, including SUDEP.

Additionally, they are working on ways that can help families become more empowered to start the discussion themselves. Materials for the waiting room or questionnaires to fill out before appointments could trigger conversations with care providers, Berl says.

Last, the team also is collaborating with a medical device company that is working on a nighttime monitoring system that could provide an alert if patients with epilepsy experience nighttime seizures, a risk factor for SUDEP. Such technologies have not been proven to prevent SUDEP. Yet, it may help caregivers get help more quickly than if they did not receive the alert.

For each of these efforts, Berl notes, having Lapham as a partner has been key. “She’s part of our meetings and has input into the direction of each project,” Berl explains. “When you have a partner who is so close to the daily work you’re doing, it just heightens those efforts and brings to the forefront the simple message of why this is important.”