PEDIATRICS Vol. 122 No. 2 August 2008, pp. 440-441 (doi:10.1542/peds.2008-1417)
COMMENTARY |
How Low Can I Go? The Impact of Hypoglycemia on the Immature Brain
Department of Pediatrics, St Louis Children's Hospital, Washington University, St Louis, Missouri
Abbreviations: EAA—excitatory amino acid
Cerebral metabolism and function depends on adequate blood glucose, which provides for >90% of cerebral energy.1 Although the newborn brain is less vulnerable than the adult brain to the immediate functional and electrophysiological impact of hypoglycemia, epidemiologic and experimental evidence has confirmed cerebral injury related to isolated hypoglycemia in the newborn brain.2 In the July 2008 of Pediatrics, Burns et al3 described the neuroimaging findings and neurodevelopmental outcomes of 35 term infants with symptomatic hypoglycemia (86% of infants with a blood glucose of <35 mg/dL).
 |
NATURE AND MECHANISMS OF CEREBRAL INJURY |
|---|
 TOP NATURE AND MECHANISMS OF... CLINICAL SIGNIFICANCEREFERENCES |
|---|
The impact of isolated hypoglycemia on the developing brain has been well documented in animal experiments, including those on primates.2,4 These experiments have defined 3 important principles in relation to hypoglycemia-mediated cerebral injury in the newborn. First, prolonged and severe, rather than transient or minor, hypoglycemia was required for cerebral injury. Second, the pattern of injury involved neuronal injury to the upper cortical layers (2 and 3), particularly affecting the parieto-occipital regions, as well as injury to the hippocampus, caudate, and white matter. Finally, mild hypoglycemia combined with mild hypoxia-ischemia resulted in cerebral injury, whereas either of the 2 conditions in isolation did not.
The human neuropathology of isolated hypoglycemia was documented more than 40 years ago in 6 infants at the Hammersmith Hospital,5 the same institution from which the Burns et al3 study originated. Only 1 infant in that study was born at term with no apparent cause of injury other than hypoglycemia. This infant had seizures from 17 hours of life, with a low blood glucose level documented at 51 hours and death resulting from aspiration at 55 hours. An autopsy documented widespread acute neuronal and glial degeneration, most severely in the occipital lobes. Moderate injury was also seen in the hippocampus, caudate, putamen, cerebellum, and spinal cord. This pattern of neuropathology differs from that of ischemic cerebral injury,6 with absence of watershed lesions and injury primarily to upper cortical layers rather than deep cortical layers.3,5,6 This pattern also differs slightly from that observed in the adult with hypoglycemic cerebral injury, in whom no brainstem or cerebellar injury is seen.7
Similarities do exist, however, across all age groups in the vulnerability of the upper cortical layers,8 which supports the theory that neuronal injury occurs more superficially from excitatory amino acids (EAAs) (eg, glutamate and aspartate) in the cerebrospinal fluid. Thus, hypoglycemic cerebral injury is mediated by both secondary injurious agents, such as EAAs, in addition to primary energy deprivation. The impact of clinical seizures occurring in the presence of hypoglycemia supports the importance of EAA-mediated brain injury. The presence of neonatal seizures in the setting of hypoglycemia is associated with a marked worsening in pathology and prognosis.2,5
To date, neuroimaging studies of isolated hypoglycemia have confirmed the relative vulnerability of the occipital region,9–11 although the mechanisms responsible for this vulnerability remain unclear. The study by Burns et al3 extends the spectrum of MRI abnormalities in the setting of hypoglycemia to the white matter, deep nuclear gray matter, and cortical infarction. The vulnerability of the cortex, caudate, and white matter is consistent with previous neuropathology. However, the greater diversity of the lesions reported by Burns et al, including watershed parasagittal lesions (n = 12), focal infarction (n = 3), and hemorrhage (n = 8), along with the absence of any relationship between the extent of hypoglycemia is in conflict with the previous literature and raises the possibility that this cohort may represent a mixture of infants displaying both isolated hypoglycemia and confounding mild hypoxia-ischemia and hypoglycemia.
|
CLINICAL SIGNIFICANCE |
|---|
|
TOPNATURE AND MECHANISMS OF...CLINICAL SIGNIFICANCEREFERENCES |
|---|
For the clinician, the experimental and human clinical data are clear that hypoglycemia (blood glucose level < 45 mg/dL), isolated or combined with mild hypoxia-ischemia, is injurious to the newborn brain and must be monitored for closely and managed aggressively to avoid adverse consequences. The study by Burns et al3 also supports the notion that MRI should be a routine investigation for the newborn infant with symptomatic hypoglycemia to define the nature of any cerebral injury.
|
FOOTNOTES |
|---|
Accepted May 19, 2008.
Address correspondence to Terrie Inder, MBChB, MD, FRACP, Washington University School of Medicine, Department of Neurology, 660 S Euclid Ave, St Louis, MO 63110. E-mail: inder_t{at}wustl.edu
The author has indicated she has no financial relationships relevant to this article to disclose.
|
REFERENCES |
|---|
|
TOPNATURE AND MECHANISMS OF...CLINICAL SIGNIFICANCEREFERENCES |
|---|
- Hernández M, Vannucci R, Salcedo A, Brennan R. Cerebral blood flow and metabolism during hypoglycemia in newborn dogs. J Neurochem. 1980;35 (3):622 –626[CrossRef][Web of Science][Medline]
- Volpe JJ. Hypoglycemia and brain injury. In: Neurology of the Newborn. 4th ed. Philadelphia, PA: WB Saunders; 2000:497–520
- Burns C, Rutherford M, Boardman J, Cowan F. Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic neonatal hypoglycemia.
Pediatrics. 2008;122
(1):65
–74
[Abstract/Free Full Text] - Brierley JB, Brown AW, Meldrum BS. The neuropathology of insulin induced hypoglycemia in primate. In: Meldrum JB, Brierley BS, eds. Brain Hypoxia. Philadelphia, PA: JB Lippincott; 1971
- Anderson JM, Milner RDG, Strich SJ. Effects of neonatal hypoglycemia on the nervous system: a pathological study.
J Neurol Neurosurg Psychiatry. 1967;30
(4):295
–310
[Free Full Text] - Banker BQ. The neuropathological effects of anoxia and hypoglycemia in the newborn. Dev Med Child Neurol. 1967;9 (5):544 –550[Web of Science][Medline]
- Auer RN. Hypoglycemic brain damage. Metab Brain Dis. 2004;19 (3–4):169 –175[CrossRef][Web of Science][Medline]
- Sandberg M, Butcher SP, Hagberg H. Extracellular overflow of neuroactive amino acids during severe insulin induced hypoglycemia: in vivo dialysis of the rat hippocampus. J Neurochem. 1986;47 (1):178 –184[Web of Science][Medline]
- Barkovich JA, Al Ali F, Rowley HA, Bass N. Imaging patterns of neonatal hypoglycemia. AJNR Am J Neuroradiol. 1998;19 (3):523 –528[Abstract]
- Filan PM, Inder TE, Cameron FJ, Kean MJ, Hunt RW. Neonatal hypoglycemia and occipital cerebral injury. J Pediatr. 2006;148 (4):552 –555[CrossRef][Web of Science][Medline]
- Yalnizoglu D, Haliloglu G, Turanli G, Cila A, Topcu M. Neurological outcome in patients with MRI pattern of damage typical for neonatal hypoglycemia. Brain Dev. 2007;29 (5):285 –292[CrossRef][Web of Science][Medline]
PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  W. W. Hay Jr, J. E. McGowan, S. Kalhan, D. Adamkin, J. M. Hawdon, A. F. Williams, L. Rosenbloom, and M. P. Ward-Platt How Low Can I Go? The Impact of Hypoglycemia on the Immature Brain Pediatrics, December 1, 2008; 122(6): 1411 - 1412. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
