Syndrome of the Trephined: Clinical Spectrum, Risk Factors, and Impact of Cranioplasty on Neurological Recovery in a Prospective Cohort

Abstract Background: Syndrome of the Trephined (SoT) is an underrecognized complication after decompressive craniectomy. We aimed to investigate SoT incidence, clinical spectrum, risk factors, and the impact of the cranioplasty on neurological recovery.Methods: Patients undergoing a large craniectomy (>80 cm2) and cranioplasty were prospectively evaluated using modified Rankin score (mRS) and cognitive (attention, processing speed, executive function, language, visuospatial neglect), motor (Motricity Index, Jamar dynamometer, postural score, gait assessment), and radiological evaluation within four days before and after cranioplasty. The primary outcome was SoT, diagnosed when a neurological improvement was observed after the cranioplasty. The secondary outcome was good outcome (mRS 0-3) four days and 90 days after the cranioplasty. Logistic regression models were used to evaluate the risk factors for SoT and the impact of cranioplasty timing on neurological recovery.Results: twenty-six patients (65%) developed SoT and improved after cranioplasty. Brain trauma, hemorrhagic lesions, and shifting of brain structures were associated with SoT. After cranioplasty, a shift towards a good outcome was observed within four days (p=0.025) and persisted at 90 days (p=0.005). Increasing delay to cranioplasty was associated with decreased odds of improvement when adjusting for age and baseline disability (odds ratio 0.96; 95% CI, 0.93-0.99 p=0.012).Conclusions: SoT is frequent after craniectomy and interferes with recovery. A high suspicion of SoT should be exercised in patients who fail to progress or have a previous trauma, hemorrhage, or shifting of brain structures. Performing the cranioplasty earlier was associated with improved and quantifiable neurological recovery.