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Background: Definite diagnosis of prion diseases or transmissible spongiform encephalopathies (TSEs) requires neuropathology, usually at autopsy. Epidemiology of human TSEs has relied on definite as well as 'probable' cases in which neuropathological confirmation is lacking, usually because of low autopsy rates in most countries., Methods: In Austria, an active surveillance program for human prion diseases was established in 1996. Since then, more than 900 referrals were analyzed. Postmortem investigation of brain tissue is mandatory in every suspect case of TSE. Thus, epidemiological data on TSEs from Austria may serve as autopsy-controlled reference for countries with lower autopsy rates., Results: The total number of TSE cases in Austria since 1969 is 206. The average yearly mortality for the active surveillance period from 1996 to 30 June 2006 is 1.39 per million, with the highest rates for Vienna (2.37) compared with other provinces. Eighty-five percent of definite TSEs were classified as sporadic Creutzfeldt-Jakob disease (sCJD). We observed a significant linear increase in the mean age at death of 0.6 years per calendar year. Clinical diagnostic surveillance criteria had a sensitivity and specificity of 82.7 and 80.0% for probable CJD, respectively, and a positive predictive value of 80.5% for probable and 38.9% for 'possible' CJD. Alternative neuropathological diagnoses in suspect cases included Alzheimer's disease with or without Lewy body pathology, vascular encephalopathy, metabolic encephalopathies and viral or limbic encephalitis., Conclusion: The steady increase in mortality rates, especially in old age groups, most likely reflects improved case ascertainment due to active surveillance causing higher awareness of the medical community. In comparison with other European countries, it is reassuring to note that the overall death rate of TSEs does not differ from the Austrian autopsy-controlled data, thus confirming the value of clinical surveillance criteria., (Copyright 2008 S. Karger AG, Basel.)

Occurrence, distribution, and phenotype of arylsulfatase A (ASA) mutations were investigated in 27 patients with metachromatic leukodystrophy (MLD) from Central Europe, mainly from Austria (n = 15) and Poland (n = 9). Genomic DNA from leukocytes, fibroblasts, or paraffin-embedded, formalin-fixed brain or nerve tissue, respectively, was tested by natural or mutated primer-modulated PCR restriction, fragment length polymorphism for the eight most common European mutations: R84Q, S96F, 459+1G > A, I179S, A212V, 1204+1G > A, P426L, and 1401del11bp. The overall identification rate of unrelated MLD alleles was the highest, in adult (90%), medium in juvenile (50%), and lowest in late infantile (36%) MLD patients. The two common alleles, 459+1G > A and P426L, together accounted for 42% of all 50 unrelated MLD alleles investigated; I179S was observed in 6 of 50 MLD alleles (12%). Thus, I179S was far more frequent than hitherto thought and appears to be a third common mutation in Europe. Moreover, a different allelic distribution between Austrian and Polish juvenile patients was disclosed, indicating genetic heterogeneity of MLD even within Central Europe. The genotype-phenotype correlation suggested by Polten et al. [N Engl J Med 324:18-22, 1991] was not followed by all of our MLD patients. Moreover, some MLD patients with identical ASA mutations presented with different phenotypes. This may be due, at least in some cases, to the presence of an additional mutation on individual mutant alleles. Therefore, prediction of the clinical course from single mutation analysis is not possible.