This case followed a biphasic clinical course of status epilepticus 5 days after TBI, revealing BTA and ipsilateral hyperperfusion the day before the late seizure. This case exhibited clinical features similar to those of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) [1, 2]. AESD is a subtype of acute infectious encephalopathy in infants with a prolonged febrile seizure, following a late seizure after 4–6 days and exhibiting BTA [2]. The pathogenesis of AESD has been considered to involve excitotoxicity with delayed neuronal death [2]. When status epilepticus occurs, excitatory neurons in the cerebral cortex release large amounts of excitatory amino acids, such as glutamate. If the quantity of glutamate released is large, the surrounding astrocytes cannot metabolize it into glutamine. This causes an influx of Ca2+ into the postsynaptic neurons, resulting in delayed necrotic cell death or apoptosis [2].
We reviewed 12 TBIRD cases [1, 3–9] (Table 1), excluding cases in which the onset of TBI was unknown or the biphasic clinical course was unclear. The median age was 9 months, and all patients were under 2 years of age. SDH was observed in all cases. The median interval of the biphasic phase was 3 days. Late seizures occurred in 11/12 cases, and 1 case presented only with unconsciousness, although non-convulsive seizures were not ruled out [1]. The median interval between BTA and TBI detection was 5 days. Only our case was detected with BTA 4 days after TBI.
Table 1
Case review of infantile traumatic brain injury with a biphasic clinical course and late reduced diffusion
| Value |
Age (month), median [IQR] | 9.0 [7.25–14.25] |
Mechanism of injury, n (%) Fall Thrown Traffic accident Unknown | 8 (67%) 1 (8%) 1 (8%) 2 (17%) |
Initial Symptoms, n (%) Convulsive Seizure Status epilepticus Unconsciousness Hemiparalysis | 8 (67%) 3 4 (33%) 6 (50%) |
Glasgow Coma Scale, n (%) ≤8 >8 Unknown | 5 (42%) 4 (33%) 3 (25%) |
Imaging findings, n (%) Subdural hemorrhage Midline shift Subarachnoid hemorrhage Diffuse axonal injury | 12 (100%) 4 1 (8%) 0 |
Initial treatment, n (%) Conservative therapy Barbiturate coma therapy Surgery | 10 (83%) 2 2 (17%) |
Day of late seizure, median [IQR] | 3 [3.0–4.0] |
Bright tree appearance on MRI Bilateral Unilateral Unknown | 8 (67%) 3 (25%) 1 (8%) |
Day of bright tree appearance on MRI, median [IQR] | 5 [3.0–5.0] |
Second treatment (after the second phase), n (%) Conservative therapy Barbiturate coma therapy Surgery | 11 (92%) 5 1 (8%) |
Cerebral atrophy, n (%) Yes No Unknown | 10 (83%) 1 (17%) 1 (17%) |
Pediatric Cerebral Performance Category Scale, n (%) ≤2 ≥3 Unknown | 4 (33%) 7 (58%) 1 (8%) |
IQR, interquartile range; CT; computed tomography, MRI; magnetic resonance imaging |
BTA has been implicated in incomplete myelination until approximately 2 years of age [1]. The developing brain is vulnerable due to immature cerebrovascular autoregulation [10], high concentrations of unsaturated fatty acids, high oxygen consumption, and low concentrations of antioxidants [10, 11]. The high density of N-methyl-D-aspartate receptors [11] may also be associated with the risk of excitotoxicity. MR spectroscopy showed elevated glutamine/glutamate complexes and decreased N-acetyl aspartate levels in AESD [2, 12, 13]. The same findings were observed in 2 cases of TBIRD [1, 7], suggesting that TBIRD is pathophysiologically identical to AESD. Some cases of TBIRD differ from AESD in that status epilepticus is not present in the initial phase. Two cases of TBIRD showed hypoperfusion in the ipsilateral cerebral hemisphere [7, 9], similar to an animal SDH model [14], suggesting a cerebral metabolic blood flow imbalance due to microvessel vasospasm [15, 16]. In contrast, our case showed hyperperfusion, which may suggest ischemia-reperfusion injury associated with impaired cerebrovascular autoregulation.
TBIRD often has a poor neurological prognosis, with PCPC ≥ 3 occurring in 58% (7/12) of cases. Although the prevention and treatment of TBIRD remain to be elucidated, the characteristics of TBIRD were shown to be infantile TBI in patients who developed SDH with unconsciousness, seizure, or hemiplegia in this study. Some patients may exhibit BTA prior to the late seizure, as in our case.