38. Understanding Syndrome of the Trephined: Balance, Coordination, and Gait Analysis After Decompressive Craniectomy in a Mouse Model of Traumatic Brain Injury

PURPOSE: Syndrome of the Trephined (SoT) is defined as neurological deterioration that occurs after a large craniectomy, with symptoms improving or completely resolving following cranioplasty. Patients with a traumatic brain injury (TBI) may be prone to developing SoT after decompressive craniectomy. Our aim is to understand the underlying pathophysiology of SoT by assessing neurological dysfunction in a new mouse model of decompressive craniectomy and cranioplasty after TBI using previously established behavioral analysis tools. METHODS: Four groups of 6 adult C57BL/6 mice were evaluated: 1) craniectomy with immediate replacement of the calvarial bone (C-R), 2) craniectomy without replacement of the calvarial bone (C-NR), 3) craniectomy + TBI with immediate replacement of the calvarial bone (C+TBI-R), and 4) craniectomy + TBI without replacement of the calvarial bone (C+TBI-NR). We utilized a controlled cortical impact model of TBI with an impact depth of 2mm. Behavioral analysis via balance beam and Treadscan was performed at baseline (prior to surgery) and at 1, 2, 3, and 4 weeks after the respective surgery to evaluate neurologic dysfunction through fine motor coordination, balance, and gait analysis. RESULTS:Balance Beam: In the first week after surgery, all groups showed a decline in performance, indicated by increased foot slips. By week two, the C-R group performance gradually improved, with performance similar to baseline by week 4. In contrast, C-NR group and both TBI groups had persistently increased foot slips across all time points. The C-NR group showed significantly increased number of footslips at week 3 and week 4 (p=0.0347, p=0.0394). Similarly, the C+TBI-R and C+TBI-NR groups showed significant increase in foot slips, especially by week 4 (p= 0.002, p= 0.0031). Treadscan: Various gait parameters at different speeds were measured. Significant differences in stance time, lateral maximum deviation, and stride length were observed at 15 cm/s. Increased stance time, increased lateral maximum deviation, and decreased stride length indicate gait abnormalities. Results showed a significant increase in stance time of the rear left foot in the C-NR group compared to the C-R group, C+TBI-R, and C+TBI-NR groups at week 4 (p=0.0058, p=0.0242, p=0.0094). There was also a significant increase in stance time of the rear right foot in the C-NR group compared to the C-R group at week 4 (p=0.0302). In week 4, the C-NR group showed significantly shorter stride lengths in the rear right foot than both groups with TBI (p=0.0421, p=0.0201). A significant increase in lateral maximum deviation of the rear right foot from the body axis was observed in the C-NR group compared to the C+TBI-R and C+TBI-NR groups at week 4 (p=0.0238, p=0.0087). CONCLUSION: The C-NR group demonstrated that lack of bone replacement following craniectomy can result in decreased balance, impaired fine motor coordination, and abnormal gait changes at higher speeds. Interestingly, these deficits were even more pronounced in the mice with TBI with or without bone replacement. Further studies are ongoing to evaluate specific gait patterns and trends in this novel mouse model to better understand the symptomatic effects and pathophysiology of SoT.