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Surrogate markers for neurological outcome in children after deep hypothermic circulatory arrest
Scott D Markowitz1, Rebecca N Ichord, Gil Wernovsky
1Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA. markowitzs@email.chop.edu
Insights
Neurodevelopmental disabilities affect up to 50% of children with complex congenital heart disease (CHD). Identifying mechanisms and surrogate markers for these outcomes is crucial for developing effective neuroprotective interventions.
Area of Science:
- Pediatric Cardiology
- Neurodevelopmental Science
- Medical Imaging
Background:
- Improved survival in infants with congenital heart disease (CHD) has shifted focus to neurodevelopmental morbidities.
- Neurologic injury in complex CHD patients can stem from various factors including genetic, hemodynamic, and prenatal issues.
- Subtle neurological deficits may manifest later in childhood, impacting speech, motor skills, and attention.
Purpose of the Study:
- To identify mechanisms underlying neurodevelopmental injuries in children with complex CHD.
- To evaluate surrogate markers for predicting long-term neurodevelopmental outcomes.
- To summarize current advancements and future directions in neuroprotection for CHD patients.
Main Methods:
- Review of existing literature on neurodevelopmental outcomes in CHD.
- Exploration of potential surrogate markers such as serologic proteins, seizures, MRI findings, cerebral oxygenation, and neurologic examination.
- Highlighting the potential of advanced MRI techniques and near-infrared spectroscopy.
Main Results:
- Up to 50% of complex CHD patients exhibit speech, motor, or attention deficits by school age.
- Current methods for identifying subtle, long-term neurological injury are limited.
- The evaluation of surrogate markers is in its early stages due to the long-term nature of outcomes.
Conclusions:
- There is a critical need to identify injury mechanisms for effective neuroprotection in CHD.
- Advanced imaging and physiological measures show promise for future research.
- Significant work remains to ensure comparable neurodevelopmental outcomes for CHD patients and their healthy peers.
Abstract:
Improved survival for infants with congenital heart disease (CHD) has led to increased focus on the most significant morbidities that are neurodevelopmental. Neurologic injury in neurodevelopmental outcome may have many causes in children with complex CHD undergoing cardiopulmonary bypass and deep hypothermic circulatory arrest, including genetic syndromes, abnormal blood flow patterns, prenatal insults, and hemodynamic instability. Although gross neurological injury can be detected in the perinatal and postoperative period, more subtle injury may not be identified until much later. Disabilities in speech and language, motor skills, and attention deficit disorder are present by school age in up to 50% of the complex CHD population. It is imperative that the mechanisms of these injuries be identified to enable the application of neuroprotective interventions. To facilitate clinical investigation, evaluation of surrogate markers for these longer term "real" outcomes continues. Because some abnormalities may not be detected for years, the evaluation of a surrogate marker takes a long time. Thus, identification of surrogate markers is in its infancy. Serologic proteins, seizures, magnetic resonance findings, cerebral oxygenation, and the neurologic examination have all been studied. Continuing innovation in the use of magnetic resonance imaging techniques and the application of physiologic measures including near-infrared spectroscopy currently pose the greatest potential for advances. This article summarizes the state of the art and an admission about how far we have yet to travel as we strive to make the neurodevelopmental outcomes of patients with CHD comparable to their healthy peers.