Surgery and Risk of Sporadic Creutzfeldt-Jakob Disease in Denmark and Sweden: Registry-Based Case-Control Studies
ABSTRACT Epidemiologic evidence of surgical transmission of sporadic Creutzfeldt-Jakob disease (sCJD) remains controversial.
From Danish and Swedish registries we selected 167 definite and probable sCJD cases (with onset between 1987 and 2003) and 3,059 controls (835 age-, sex-, and residence-matched, and 2,224 unmatched). Independent of case/control status, surgical histories were obtained from National Hospital Discharge Registries. Surgical procedures were categorized by body system group and lag time to onset of sCJD. Exposure frequencies were compared using logistic regression.
A history of any major surgery, conducted >/=20 years before sCJD onset, was more common in cases than both matched (OR = 2.44, 95% CI = 1.46-4.07) and unmatched controls (OR = 2.25, 95% CI = 1.48-3.44). This observation was corroborated by a linear increase in risk per surgical discharge (OR = 1.57, 95% CI = 1.13-2.18; OR = 1.50, 95% CI = 1.18-1.91). Surgery of various body systems, including peripheral vessels, digestive system and spleen, and female genital organs, was significantly associated with increased sCJD risk.
A variety of major surgical procedures constitute a risk factor for sCJD following an incubation period of many years. A considerable number of sCJD cases may originate from health care-related accidental transmission.
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ABSTRACT: Genetic human prion diseases are autosomal dominant disorders associated with different mutations in the PRNP gene that are manifested as distinct clinical phenotypes. Here, we report a new pathogenic missense mutation (c.[643A>G], p.[I215V]) in the PRNP gene associated with three pathologically confirmed cases: two of Creutzfeldt–Jakob disease (CJD) and one of Alzheimer’s disease (AD) in two different families from the same geographical region in Spain. This mutation has not been found in any of more than 2,000 control cases studied. It represents a conservative amino acid change, and the same change is observed in the PRNP gene from other species. The two CJD cases were homozygous at codon 129 (M/M), but showed divergent clinical phenotypes with onset at ages 55 and 77 years and illness durations of 15 and 6 months, respectively. The postmortem neuropathological analysis of these cases showed homogeneous features compatible with CJD. Interestingly, the AD case (a brother of one of the CJD cases) was heterozygous at codon 129 (M/V). No familiar history was documented for any of the cases, suggesting a de novo mutation, or a partial, age-dependent penetration of the mutation, perhaps related to codon 129 status. This new mutation extends the list of known pathogenic mutations responsible for genetic CJD, reinforces the clinical heterogeneity of the disease, and advocates for the inclusion of PRNP gene examination in the diagnostic workup of patients with poorly classifiable dementia, even in the absence of family history.Journal of Neurology 01/2012; 260(1). DOI:10.1007/s00415-012-6588-1 · 3.84 Impact Factor
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ABSTRACT: Sporadic Creutzfeldt-Jakob disease (sCJD) might be transmitted by surgery. The purpose of this study was to investigate potential susceptibility to sCJD from surgery at juvenile age and in early adulthood.PLoS ONE 10/2014; 9(10):e109412. DOI:10.1371/journal.pone.0109412 · 3.53 Impact Factor
The Medical journal of Australia 10/2013; 199(8):535-6. DOI:10.5694/mja13.10475 · 3.79 Impact Factor