Abstract
BackgroundThe function of the autonomic nervous system can be assessed by determining heart rate variability (HRV), which is impaired in some brainstem diseases in humans. Transmissible spongiform encephalopathies (TSEs) in sheep are diseases characterised by accumulation of disease-associated prion protein in the brainstem, including nuclei of the parasympathetic nervous system. This study was undertaken to assess whether analysis of HRV can be used as an aid in the diagnosis of TSEs in clinically affected, naturally or experimentally infected sheep.FindingsWhen HRV indices were compared between 41 clinical TSE cases (18 sheep infected with scrapie and 23 sheep infected with bovine spongiform encephalopathy), 11 control sheep and six sheep reported as scrapie suspects or dosed with BSE brain homogenate, which were not confirmed as TSE cases by postmortem tests, no significant differences were found between the groups. Median heart rate was significantly different but only when sheep were grouped by gender: it was higher in female TSE cases than in control sheep and higher in female than castrated male ovine classical BSE cases.ConclusionsHRV analysis was not useful as a diagnostic aid for TSEs of sheep.
Highlights
The function of the autonomic nervous system can be assessed by determining heart rate variability (HRV), which is impaired in some brainstem diseases in humans
Transmissible spongiform encephalopathies (TSEs) in sheep, such as scrapie or experimental bovine spongiform encephalopathy (BSE), are characterised by the accumulation of disease-associated prion protein (PrPsc) in the brainstem, in the parasympathetic nucleus of the vagus nerve [1,2], which is used for the confirmatory immunohistochemical diagnosis of these prion diseases
The function of the parasympathetic and sympathetic nervous system can be assessed by measuring heart rate variability (HRV), either by calculation of indices using statistical methods on R-R intervals or by spectral analysis of an array of R-R intervals derived from an electrocardiogram (ECG) [5]
Summary
Transmissible spongiform encephalopathies (TSEs) in sheep, such as scrapie or experimental bovine spongiform encephalopathy (BSE), are characterised by the accumulation of disease-associated prion protein (PrPsc) in the brainstem, in the parasympathetic nucleus of the vagus nerve [1,2], which is used for the confirmatory immunohistochemical diagnosis of these prion diseases. There were no significant differences for any of the indices between the groups (P > 0.05, Kruskal-Wallis one-way ANOVA, GraphPad Prism) and the ranges overlapped This was in contrast to a previous study of HRV in scrapie-infected sheep based on accumulation of PrPsc in recto-anal muscosa-associated lymphoid tissue, which described significant differences for the low frequency band between biopsy-positive and negative sheep even though the ranges between groups overlapped [9]. When separated by TSE type (classical scrapie versus classical BSE), BSE-affected female sheep had the highest median heart rate (106 bpm, range: 84-135; 13 sheep) compared to controls, which was significant (P = 0.02, Kruskal-Wallis one-way ANOVA with Dunn’s multiple comparison test, GraphPad Prism), and scrapieaffected sheep (101 bpm, range: 74-175 bpm; 17 sheep); see Figure 1. When we used similar ranges in the current study (limited by the equipment to 0.03-0.14 Hz for the low frequency band), the results did not differ (data not shown)
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