Effect of Cranioplasty Timing on Balance and Motor Coordination in a Model of Syndrome of the Trephined

PURPOSE: Syndrome of the Trephined (SoT) involves neurological decline following segmental skull removal, that improves following cranioplasty. Decompressive craniectomy (DC) after TBI is frequently associated with SoT in patients. Cranioplasty repairs skull defects, protects the brain, improves aesthetics, and improves neurological function in SoT. This study uses a mouse model of decompressive craniectomy to examine SoT’s neurological impact and the role of cranioplasty timing after traumatic brain injury (TBI). METHODS: Adult C57BL/6 mice underwent craniectomy, with the calvarial bone cryopreserved and replaced in an early cranioplasty (ECP) at 2 weeks or delayed cranioplasty (DCP) at 10 weeks. Groups included: 1) ECP, 2) DCP, 3) TBI+ECP, and 4) TBI+ DCP. This study utilized a controlled cortical impact model of TBI, with an impact depth of 2mm. Balance and fine motor coordination were evaluated through balance beam testing at baseline and at weekly time points from 1 to 16 weeks after their craniectomy surgery. RESULTS: As expected, all groups exhibited motor deficits in the early post-operative period. By week 4, the ECP group had nearly returned to baseline performance, while the DCP group continued to decline, experiencing significantly more foot slips from weeks 4 to 10 (p < 0.02). Between weeks 2 and 10, there was no significant difference in foot slips between the DCP and TBI+DCP groups, indicating that the lack of calvarial bone replacement leads to neurological dysfunction in balance and fine motor coordination, regardless of the presence of traumatic brain injury (TBI). However, following delayed cranioplasty at week 10, the DCP group showed marked improvement compared to the ECP group, highlighting the benefits of cranioplasty. Overall, the TBI groups performed worse than the non-TBI groups, regardless of cranioplasty. Interestingly, TBI+ECP mice had significantly more foot slips than TBI+DCP mice for 10 out of 16 weeks, peaking at week 8 (p = 0.0086). CONCLUSION: A key feature of the Syndrome of the Trephined is the improvement of neurological symptoms, such as balance and motor coordination, following cranioplasty. In this study, we demonstrate using a novel mouse model that cranioplasty can resolve these deficits even in the absence of traumatic brain injury (TBI), at both early and delayed time points. However, in cases of TBI, mice that underwent early cranioplasty performed worse, suggesting that premature bone replacement may hinder neurological recovery if brain swelling has not fully resolved. Ongoing studies aim to determine the optimal timing for cranioplasty after TBI, with the goal of maximizing recovery from TBI while alleviating symptoms associated with the Syndrome of the Trephined.