Via Research Recognition Day Program VCOM-Carolinas 2025

Case Reports

Hypoglycemic Encephalopathy with Multi-System Organ Dysfunction in an Infant Brianna Stein, OMS III 1 ; Rylee Simons OMS, IV 1 ; Hanna S. Sahhar, MD 1,2 ; Sami Rishmawi, MD 1,2 1 Edward Via College of Osteopathic Medicine, Carolinas Campus, Department of Pediatrics, Spartanburg, SC 2 Spartanburg Regional Healthcare System, Department of Pediatrics, Pediatric Intensive Care Unit, Spartanburg, SC Introduction Results

Discussion

Hypoglycemia is a common pediatric emergency with diverse symptoms and variable etiologies. While neonatal hypoglycemia is better understood, cases in older infants are less studied. For example, a 2-day old neonate with refractory hypoglycemia due to maternal gestational diabetes exhibited seizures and MRI findings of diffuse brain injury, similar to our patient. Current medical literature suggests a specific pattern on brain injury and long-term deficits in neonatal hypoglycemia with posterior-predominant patterns of brain injury occurring as well as underlying white matter tracts, corpus callosum, and thalamus. Our case presents the unique MRI findings of bilateral, symmetric diffusion restriction involving the caudate heads, globus pallidi, thalami, ventral cerebral peduncles, and hippocampi, without involvement of the cortex or corpus callosum. These findings suggest that infants may exhibit unique patterns of brain injury following hypoglycemic events and could have neurodevelopmental outcomes that differ from those observed in neonates. Additionally, neurodevelopmental predictions from studies focused on neonatal encephalopathy may not reliably reflect the long-term deficits in older infants. Infants and young children utilize glucose at a rate 2-3 times higher per kilogram of body weight compared to adults, due to their larger brain-to-body ratio. One study demonstrated that children under 4 have limited fasting tolerance, often developing hypoglycemia and hyperketonemia after overnight fasting with younger children experiencing a more rapid rise in ketone levels and a quicker decline in plasma glucose levels compared to older children. If this patient did not receive adequate caloric intake due to illness or insufficient breastfeeding, he was at heightened risk for hypoglycemia and ketoacidosis. Although neonates with hypoglycemia show similar presentations to our patient, there is limited research on profound hypoglycemia in older infants leading to encephalopathy and neurologic deficits. This underscores the need for further investigation into the effects of hypoglycemia in older infants and its long-term outcomes. ❑ Prompt recognition and treatment of hypoglycemia are critical to prevent long-term sequelae. Although rare endocrine and metabolic disorders can lead to severe hypoglycemia, guardians should be educated on avoidable risks such as prolonged fasting or malnutrition. ❑ Caregivers should be made aware of metabolic changes that can occur during concurrent illness – that may also place patients at risk for hypoglycemia. Encouraging frequent and adequate feeding is necessary in infants. ❑ In the event of encephalopathy, counseling should be provided to address neurodevelopmental outcomes and emphasize the importance of close follow up care. Conclusions 1. Tam EW, Haeusslein LA, Bonifacio SL, Glass HC, Rogers EE, Jeremy RJ, Barkovich AJ, Ferriero DM. Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy. J Pediatr. 2012 Jul;161(1):88-93. doi: 10.1016/j.jpeds.2011.12.047. Epub 2012 Feb 4. PMID: 22306045; PMCID: PMC3346850 2. Burns CM, Rutherford MA, Boardman JP, Cowan FM. Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic neonatal hypoglycemia. Pediatrics. 2008 Jul;122(1):65-74. doi: 10.1542/peds.2007-2822. PMID: 18595988. 3. Merel R. van Veen, Peter M. van Hasselt, Monique G. M. de Sain-van der Velden, Nanda Verhoeven, Floris C. Hofstede, Tom J. de Koning, Gepke Visser; Metabolic Profiles in Children During Fasting. Pediatrics April 2011; 127 (4): e1021 – e1027. 10.1542/peds.2010-1706 4. Ghosh, A., Banerjee, I., & Morris, A. A. M. (2016, June 1). Recognition, assessment and management of hypoglycaemia in childhood. Archives of Disease in Childhood. https://adc.bmj.com/content/101/6/575.long Acknowledgments No relevant financial affiliations or conflicts of interest. If the authors used any personal details or images of patients or research subjects, written permission or consent from the parent (or legal guardian) was obtained. The authors would like to acknowledge and thank Dr. Carol Kooistra, neurologist for assisting in the care of this patient and providing a valuable insight on the condition. References

Hypoglycemia is a medical emergency that can cause seizures, neurologic damage, organ failure or death if untreated. In infants, hypoglycemia can result from various causes, including metabolic disorders, endocrine disorders, drug ingestion, or inadequate nutrition, all of which warrant thorough investigation. Due to already low glycogen stores, severe acute malnutrition can instigate hypoglycemia in infants. Symptoms range from weakness, pallor, seizures, coma, and encephalopathy. These symptoms can potentially lead to long-term neurocognitive and motor deficits. Neonatal hypoglycemia studies show diffuse brain injury with the most severe damage occurring to the parieto-occipital lobes and underlying white matter tracts, as well as the corpus callosum, and thalamus. We report a healthy, full term, unvaccinated, 8 month-old male presenting for unresponsiveness and was found to have profound hypoglycemia of unknown origin leading to encephalopathy, anoxic brain injury and multi-system organ failure.

Electroencephalogram (EEG) revealed moderate diffuse slowing of background rhythms consistent with diffuse encephalopathy, but no focal slowing or epilepiform activity. During admission, the patient experienced recurrent hypoglycemia, prompting a critical blood draw to assess insulin, C-peptide, free fatty acids, growth hormone, cortisol, ammonia, lactate, beta-hydroxybutyrate, acylcarnitine profile, free and total carnitine, and urine organic acids. Neurofilament light chain was also drawn as a biomarker for neuronal injury. Significant results are included below in Table 1. Repeat CT scan on day 4 showed no new abnormalities, and some possible improvement of the gray/white matter differentiation at the hemispheres compared to the MRI, but also showed persistent damage (Figure 3).

Case Report

An 8-month-old full term, unvaccinated male patient with no medical history presented to the emergency department (ED) due to unresponsiveness. His mother reported 3 days of flu-like symptoms including fever, loss of appetite, and vomiting. The patient, exclusively breastfed, had no recent travel, sick contacts, or trauma. Emergency medical services (EMS) reported a blood glucose level of <10 mg/dL (70 - 100mg/dL) in which he received D10 and glucagon via IO, stabilizing his glucose to 105 mg/dL prior to ED arrival. In the ED, he was afebrile, but lethargic, with seizure-like activity including left gaze deviation and twitching of his right hand for which he was given Ativan. A non-contrast head CT showed no acute changes (Figure 1). The patient was admitted to the pediatric intensive care unit (PICU) in which a lumbar puncture (LP) was performed. Initial laboratory investigations were significant for metabolic acidosis. He received vitamin K and fresh frozen plasma due to anemia and coagulation profile values. The patient’s labs indicated multi-system organ failure due to hypoglycemia and hypoxia. Blood and CSF cultures showed no growth. Significant results are included in Table 1. Troponin was elevated at 31 pg/ ml. Brain MRI revealed evidence of encephalopathy typically occurring in the setting of anoxic brain injury or metabolic encephalopathies (Figures 2A, B).

Table 1: Laboratory investigation results.

Figure 3: Repeat axial non contrast CT showing persistent symmetric hypodense foci at the inferior basal ganglia, approximately the genu of the internal capsule consistent with the MRI appearance. These could be possible small infarcts.

While in the PICU, the patient received occupational, speech and physical therapy. Nasogastric (NG) tube feedings were initiated due to aphagia and aspiration risk. With speech and lactation support helping, the patient relearn to breastfeed. By discharge, he could tolerate oral milk. While there were neurological improvements, significant deficits persisted; he was unable to tolerate solid foods and could not sit upright without support. The full extent of the damage will likely be unknown for many years. He was referred to outpatient occupational, speech and physical therapy, as well as pediatric neurology.

Figure 2A: Axial diffusion-weighted image showing relatively bilateral and symmetric diffusion restriction involving the caudate heads, globus pallidi, thalami, ventral cerebral peduncles, and hippocampi.

Figure 2B: Axial T2-weighted image showing areas of hyperintensity associated with the regions with diffusion restrictions in Figure 2A.

Figure 1: Initial axial noncontrast CT showing no acute intracranial abnormalities.

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