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.

[Early diagnosis and treatment of Alzheimer's disease. Implementation in the doctor's office]. / Frühdiagnostik und Therapie der Alzheimer-Krankheit. Zum Vorgehen in der Praxis.

The efficacy of antidemential agents proven in comprehensive studies and by clinical experience, now justifies an active and positive approach by the general physician to the diagnosis and treatment of patients with dementia. The proposals on how to implement diagnostic and therapeutic measures in the doctor's office comply both with medical quality criteria and the requirements for appropriateness of treatment and considerations of economy stipulated by German law. They therefore provide the basis for a modern diagnostic work-up and treatment strategy, which will also meet economical demands.

NGF content in the cerebral cortex of non-demented patients with amyloid-plaques and in symptomatic Alzheimer's disease.

There is increasing evidence that in Alzheimer's disease nerve growth factor (NGF) protein and NGF mRNA content in postmortem cortex is not decreased, but may even be elevated although the NGF-sensitive cholinergic basal forebrain neurons are preferentially affected. However, only little is known about the early pathophysiological events leading to Alzheimer's disease. We therefore measured the post-mortem NGF concentrations in temporal and frontal cortex of Alzheimer's disease patients, non-demented controls without Alzheimer's disease-related pathology, as well as non-demented patients with beta A4 plaques who might be classified as 'preclinical' cases. In the Alzheimer's disease group we found up to 43% increase in NGF concentrations in the frontal and temporal cortex as compared to the two other groups. In a subgroup analysis of the non-demented patients with plaques, NGF concentrations were lower in the frontal cortex when beta A4 plaques were present (46% of the control temporal area) than in patients without evidence of frontal plaques (81% of the control temporal area). This NGF decrease was paralleled to a similar decrease of choline acetyltransferase activity, which is regulated by NGF in the cholinergic basal forebrain. These findings support the hypothesis of lower cortical NGF content at the onset of plaque formation and of elevated NGF levels in the clinically manifest and neuropathologically advanced stage of the disease.