We present a novel large German kindred of fatal familial insomnia (FFI) consisting of three branches and comprising more than 800 individuals of 12 generations, the largest pedigree of any familial prion disease known today. There is a wide spectrum of clinical presentations leading to misdiagnoses of Olivo-Ponto-Cerebellar Atrophy (OPCA), Parkinson's or Alzheimer's disease in addition to Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Molecular genetic analysis of the prion protein gene (PRNP) confirmed the mutation D178N segregating with methionine at the polymorphic codon 129 of PRNP in all 7 patients examined. This polymorphism at codon 129 is supposed to discriminate between familial CJD (fCJD) and FFI; the 129M allele determines FFI and 129V fCJD. Furthermore, heterozygosity at this site appears to induce prolonged disease duration as compared to the homozygous condition. The variability of the clinical and pathological findings documented for our patients indicates the difficulty in establishing the diagnosis of FFI on clinical and on pathological grounds alone. In three cases (IX-97, XI-21, V-2) followed up by us prospectively insomnia was an early and severe symptom; however, in case notes analyzed retrospectively this symptom was frequently missed. In contrast to previous reports and in agreement with recent studies we cannot confirm a clear relationship between the status of the M/V polymorphism at codon 129 and the age-of-onset of this disease.

We report on two cases of brain tumour and discuss the possible relationship to previous cortical trauma. The first patient, a 67-year-old male patient developed a glioblastoma at the same site of an open shell-splinter injury of the brain after a latency of 48 years. The second patient, a 55-year-old male, had a malignant anaplastic astrocytoma in the right frontal lobe 10 years after clipping of an aneurysm of the anterior communicating artery. Both cases fulfill the criteria of Zülch [52] for the correlation between cortical trauma and tumour. We believe that the development of a brain tumour following a cortical injury is very rare, although possible. Probably the brain must display some form of predisposing genetic alteration for a tumour to develop following a cortical injury.

Despite the beneficial effect of systemic fibrinolysis in treatment within 3 hours from ischemic stroke onset, the unpredicted occurrence of intracerebral hemorrhage remains a risk from such therapy. Few data exist defining patients at risk for this outcome. We report clinical and neuropathological data on a patient fulfilling NINDS rt‐PA study and ECASS‐2 inclusion criteria with an acute stroke due to high‐grade carotid artery stenosis and preceded by amaurosis fugax. He died from an intracerebral hemorrhage after systemic fibrinolysis. The fatal outcome adds support to recommendations that rapid Doppler‐sonographic evaluation of the extra‐ and intracranial vascular status be undertaken before systemic rt‐PA is implemented in acute ischemic stroke.