Syndrome of the trephined: from pathophysiology to cranioplasty - an updated narrative review

Syndrome of the Trephined (SoT), also known as sinking skin flap syndrome, is a potentially reversible neurological complication following decompressive craniectomy (DC). It presents with a wide spectrum of clinical manifestations, including cognitive decline, psychiatric disturbances, and motor impairments. The underlying pathophysiology is multifactorial, involving reduced cerebral perfusion, altered cerebrospinal fluid dynamics, and mechanical deformation of the unprotected brain due to atmospheric pressure.

This review aims to synthesize current evidence on the clinical outcomes of SoT and to evaluate the impact of cranioplasty timing, diagnostic approaches, and emerging therapeutic strategies on patient recovery.

A narrative review of the literature was conducted, focusing on studies addressing the pathophysiology, risk factors, neuroimaging findings, and clinical outcomes of SoT. Relevant articles were identified from peer-reviewed sources and analyzed qualitatively.

Cranioplasty remains the definitive treatment for SoT, with substantial evidence demonstrating neurological and functional improvement following restoration of cranial integrity. Early surgical intervention is consistently associated with improved recovery outcomes. Advanced neuroimaging modalities, including perfusion computed tomography, magnetic resonance imaging, and functional MRI, have revealed reversible hypoperfusion and disrupted neural networks, supporting the importance of timely diagnosis and intervention. However, variability persists in diagnostic criteria, optimal timing of cranioplasty, and implant selection.

SoT is an underrecognized but treatable condition with implications for neurological functional recovery. While current management is based on clinical observations and case studies, a diagnostic framework can aid in the classification of SoT as definite, probable, or possible cases. Based on the discussion of the timing of cranioplasty after TBI, a risk-based pathway can help to determine which patients with SoT should be prioritized for cranioplasty. Additionally, a minimum dataset for reporting SoT cases will allow for the comparison of outcomes from future studies. In all patients with SoT, early identification and cranioplasty are key factors in optimizing outcomes. Although cisternostomies have been performed in patients with SoT, the low quality of evidence and lack of benefit compared to decompressive craniectomy prevents any recommendations for their use in the prevention of SoT. Finally, through a multidisciplinary approach to the care of patients with SoT, the framework proposed can be tested in future studies to validate these hypotheses.