Relationship between clinical signs and postmortem test status in cattle experimentally infected with the bovine spongiform encephalopathy agent

Based on the display of selected behavioural, sensory and locomotor changes, 20 (67%) orally dosed and 17 (77%) intracerebrally inoculated pathologically confirmed BSE cases and 21 (13%) orally dosed and 18 (6%) intracerebrally inoculated but unconfirmed cases were considered clinical BSE suspects. None of 103 controls showed significant signs and were all negative on diagnostic postmortem examinations. Signs indicative of BSE suspects, particularly over-reactivity and ataxia, were more frequently displayed in confirmed cases with vacuolar changes in the brain. The display of several BSE-associated signs over time, including repeated startle responses and nervousness, was significantly more frequent in confirmed BSE cases compared to controls, but these two signs were also significantly more frequent in orally dosed cattle unconfirmed by postmortem examinations.The findings confirm that in experimentally infected cattle clinical abnormalities indicative of BSE are accompanied by vacuolar changes and PrPd accumulation in the brainstem. The presence of more frequently expressed signs in cases with vacuolar changes is consistent with this pathology representing a more advanced stage of disease. That BSE-like signs or sign combinations occur in inoculated animals that were not confirmed as BSE cases by postmortem examinations requires further study to investigate the potential causal relationship with prion disease.Classical BSE is a prion disease of domesticated cattle presenting as a slowly progressive neurological disorder [1]. Signs associated with BSE, which comprise abnormalities of behaviour, sensation and locomotion, have been assessed as part of the passive surveillance in the UK to define the clinical phenotype of BSE [2,3]. Based on more detailed examinations and observations of BSE field cases, specific clinical protocols have been developed to aid in the clinical diagnosis of BSE field suspects [4-6] and to monitor clinical onset and progression in cattle e