Abstract: Background: Syndrome of the trephined is a well-recognised phenomenon that occurs in patients following a craniectomy. It is associated with several symptoms, including headaches, motor impairments, cognitive disorders and reduced consciousness. Treatment for the syndrome usually involves replacing the skull defect. Case Study: A 71-year-old male underwent a left-sided craniectomy after being diagnosed with biopsy-confirmed invasive squamous cell carcinoma with associated skull erosion. Subsequently, he developed a severe case of syndrome of the trephined (SoT,) resulting in having to lie flat to prevent the motor component of the Glasgow Coma Score (GCS) falling from M5/6 (E3/4 Vt M5/6) to M1 (E3/4 Vt M1) on sitting to 30 degrees. Unfortunately, due to ongoing chest sepsis and physical frailty, he was unable to undergo a cranioplasty. Therefore, to aid in clinical stabilisation, the treating physicians and clinical engineering teams designed and manufactured a prosthesis on-site, allowing rapid patient treatment. The prosthesis led to the patient being able to sit up to 30 degrees without the motor component of the GCS falling from M6 to M1 (E4 VT M6). Conclusion: Clinical improvements were demonstrated with definitive neurological improvement after applying the external cranial plate in clinical outcome measures and radiographically. Furthermore, we have shown that rapid prototyping technology provides a flexible solution to synthesise bespoke medical prostheses with the correct expertise and regulatory framework.