- Massachusetts General Hospital researchers previously created the first animal model of hemispheric hypodensity (HH), a radiologic injury pattern associated with subdural hematoma (SDH) often in young children who have suffered abusive head trauma
- In this new study, patterns of injury in the model were similar to those in human children—SDH and HH were bilateral in "infant" piglets, unilateral in "toddler" piglets—and hemorrhage on the cortex directed the location of damage to the cortex
- Prolonged seizures drove neural damage in toddlers, but infants seemed resistant to seizure-induced damage, suggesting it may be possible to identify therapeutic targets to reduce the spread of damage
- Work is currently underway at Mass General to develop age-specific therapies for preventing injury progression after severe abusive head trauma
Subdural hematoma is the most common intracranial finding after abusive head trauma. Hemispheric hypodensity (HH), a radiologic injury pattern unique to infants and toddlers, is observed in up to 50% of child victims of abusive head trauma admitted to a pediatric ICU. Associated with a doubled risk of death, HH develops in the hemisphere(s) underlying the SDH, encompasses multiple vascular territories and is later followed by severe cortical atrophy and significant disability. HH has been observed after witnessed accidents.
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In unilateral HH (restriction of SDH and hypodensity to one hemisphere), children often have overt or subclinical seizures during the acute period along with episodes of apnea and hypoventilation. There is no therapy.
As described in the Journal of Neurotrauma, researchers at Massachusetts General Hospital previously created an experimental model of unilateral HH in piglets aged 1 month (comparable to human toddlers, "toddler"). In further research using the same model, Beth Costine-Bartell, PhD, principal investigator of the Brain Trauma Lab in the Department of Neurosurgery at Mass General, and colleagues are probing the pathophysiology of unilateral HH.
In their latest work, published in Neurobiology of Disease, the researchers found that extensive damage requires a perfect storm of hemorrhage pattern and prolonged seizures, and clinical effects and patterns of damage are age-dependent.
The researchers alternately assigned "infant" or "toddler" piglets to undergo sham surgery or surgery to create HH model injuries while anesthetized. The injuries were made to the right hemisphere: cortical impact, mass effect, placement of SDH, seizure induced by kainic acid, one minute of apnea and 10 minutes of hypoventilation.
Piglets that received model injuries required critical care with sedation overnight because of depressed neurologic function. All animals had electroencephalograms recorded, then were euthanized 24 hours after injury for examination of the brain.
In "infants", the pattern of damage was patchy in both hemispheres. If there was no significant SDH, then the hippocampus was damaged instead of the cortex.
In "toddlers", the damage spread from the site of the cortical impact along the cortical ribbon in the right hemisphere spanning multiple vascular territories. The deep gray matter, hippocampus and left hemisphere were spared.
Thus, hemorrhage on the cortex appears to direct the location of the damage to the cortex. Sparing of the contralateral hemisphere shows the injury is not purely due to hypoxia.
The pattern of SDH distribution is similar in humans, where infants often have bilateral SDH and HH, and toddlers more often have unilateral SDH and HH.
Effect of Seizures
Since seizures are induced in this model, their effect can be measured apart from the severity of other injuries. Seizure duration was not different between age groups, suggesting how the brain responds to seizures may be the key difference between developmental stages:
- Infants had less damage that was not correlated to seizures
- Toddlers had extensive damage positively correlated to seizure duration; the unilateral pattern of damage was observed only in those with seizures lasting over one hour
Thus, prolonged seizures appear to drive damage in brain tissue that is already compromised with hemorrhage, focal trauma and mass effect.
Other Clinical Effects
Lactate increased and pH fell similarly in infants and toddlers, but infants continued to display metabolic acidosis before euthanasia. Infants had lower neurologic scores than toddlers eight hours after injury and remained reliant on the ventilator. In contrast, some toddlers were extubated overnight.
The injuries in this model seem to work synergistically to cause a cascade of extensive tissue destruction after abusive head trauma. Work is underway at Mass General to understand if seizures only or seizures with SDH and SAH are sufficient to induce this patter and to develop age-specific therapies that prevent the progression of such damage in young children.
The model should also prove useful to improve clinical management in the pediatric intensive care unit.
Learn more about the Pediatric Neurosurgery service at Mass General
Refer a patient to the Department of Neurosurgery