Proceedings of The Physiological Society

Trinity College Dublin (2003) J Physiol 551P, C47

Communications

Symptomatic vCJD alters heart rate variability

L.A.M. Woolfson*, D.G. Glover†, B.J. Pollard*† and Chris J.D. Pomfrett*

University Department of Anaesthesia, * University of Manchester, † Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK


Ante-mortem diagnosis of variant Creutzfeld Jacob disease (vCJD) is based on the subjective assessment of clinical signs, sometimes combined with invasive biopsy for the presence of infectious prion protein (PrPsc) in the tonsils. Post mortem diagnosis of transmissible spongiform encephalopathies in animals routinely depends on the microscopic immunohistochemical identification of PrPsc in the medulla oblongata of the brainstem (Wells et al. 1989), and in particular the nucleus tractus solitarii (NTS) and the dorsal vagal nucleus (DVN), the vagus nerve being a suspected route of infection in some species (Beekes et al. 1998). It has already been suggested that symptomatic bovine spongiform encephalopathy is associated with disturbance in heart rate variability (HRV) (Pomfrett & Austin, 1997), possibly occurring as a result of functional changes in NTS and DVN in the presence of PrPsc, and we sought to determine whether this is also the case in humans exhibiting symptoms of vCJD.

Data were collected in accordance with a protocol approved by the North West Multi Centre Research Ethics Committee, including written, informed consent. Three-hundred-second samples of electrocardiogram (ECG) were collected at repeated intervals during a 3-month period from two subjects exhibiting definite clinical signs of vCJD, and who had also been confirmed as carrying PrPsc by tonsil biopsy. Control data were collected from seven healthy volunteers of comparable age not taking medication and with no relevant medical history. The ECG was digitised using a portable monitor (Fathom, Amtec Medical) at 1 kHz frequency and 12 bit resolution. Data were transferred to a PC, translated and analysed using standard software (CED Spike2 v4.02). The ECG waveform was reviewed by eye and artefacts rejected. Tachygrams of instantaneous ECG R-wave frequency were obtained in order to determine power spectra. Interval histograms of the R-R wave intervals were also plotted (see Fig.1). Non-parametric statistics were applied (SPSS v10.1).

We observed that symptomatic vCJD disturbed HRV. There was a significant difference in the variances of ECG R wave intervals between controls and vCJD suspects (Kruskal-Wallis H test, P < 0.001). Frequency histograms obtained from controls described normal distributions (Kolmogorov-Smirnov test, P < 0.05) whereas some frequency histograms of vCJD suspects demonstrated high levels of kurtosis, with significantly greater numbers of ECG R wave intervals in a narrow band between 0.9 and 0.98 s (Kruskal-Wallis test, P < 0.05). There was no significant difference between the mean heart rates of the two groups. Power spectral analysis revealed a significant increase in low frequency HRV (0-0.05 Hz) between the vCJD suspects and controls (Mann-Whitney U test, P < 0.05).

Further work is needed with a much larger sample size. However, this study allows us to suggest that measurement of HRV has potential as a non-invasive aid to the diagnosis of vCJD.

This study was funded by the Department of Health.

Where applicable, experiments conform with Society ethical requirements