Early age of onset in fatal familial insomnia. Two novel cases and review of the literature.

Fatal familial insomnia (FFI) is a prion disease exhibiting the PRNP D178N/129M genotype. Features of this autosomal dominant illness are progressive insomnia, dysautonomia, myoclonus, cognitive decline and motor signs associated with thalamic nerve cell loss and gliosis. In contrast to the new variant of Creutzfeldt-Jakob disease (vCJD) the onset of FFI is in middle to late adulthood. We report two male patients who belong to a large German FFI kindred. They were examined clinically, and postmortem neuropathological examination was carried out in collaboration with the German reference centre for prion disease. Additionally, the prion protein gene (PRNP) was analysed. To identify further patients with disease onset under 30 years of age a comprehensive literature review was carried out. Two male patients presented with typical symptoms of FFI at the age of 23 and 24 years. In their kindred, the age of onset has never before been under 44 years of age. Our literature review identified five additional early onset cases who died at age 21 to 25 years. In all 22 reviewed FFI families the median manifestation age was 49.5 years. Although phenotypic variability of FFI is common, age of onset under 30 years has been considered to be a hallmark of vCJD with a mean manifestation at 27 years of age. Our findings underline that in addition to vCJD, FFI must be considered in cases of young-onset prion disease. This has considerable impact on clinical management and genetic counselling.

Computer aided planning device for preoperative bending of osteosynthesis plates.

In craniofacial surgery bone fractures and repositioned bone segments often have to be fixed by titanium miniplates. In clinical routines the surgeon has to fit each miniplate t be used to the individual bone structure of the patient: bending and fitting of a miniplate must frequently be repeated several times. Often up to twenty minutes are required to achieve the best fit of a single osteosynthesis plate. As a patient usually receive several miniplates for bone fixture, he will be exposed to long anaesthesia. In co-operation with the surgeons of the Clinic of Maxillofacial surgery at the University of Heidelberg we have conceived a planning system for the preoperative positioning of miniplates on a model of the patient's skull. The appropriate bending is computed and the bending data are stored for later use by a bending device and an intraoperative positioning aid. The principles of our computer-aided tool are presented in this paper.