Quantitative EEG parameters correlate with the progression of human prion diseases

Abstract

Background: Prion diseases are universally fatal and often rapidly progressive neurodegenerative diseases. EEG has long been used in the diagnosis of sporadic Creutzfeldt-Jakob disease; however, the characteristic waveforms do not occur in all types of prion diseases. Here, we re-evaluate the utility of EEG by focusing on the development of biomarkers. We test whether abnormal quantitative EEG parameters can be used to measure disease progression in prion diseases or predict disease onset in healthy individuals at risk of disease.

Methods: In the National Prion Monitoring Cohort study, we did quantitative encephalography on 301 occasions in 29 healthy controls and 67 patients with prion disease. The patients had either inherited prion disease or sporadic Creutzfeldt-Jakob disease. We computed the main background frequency, the α and θ power and the α/θ power ratio, then averaged these within 5 electrode groups. These measurements were then compared among participant groups and correlated with functional and cognitive scores cross-sectionally and longitudinally.

Results: We found lower main background frequency, α power and α/θ power ratio and higher θ power in patients compared to control participants. The main background frequency, the power in the α band and the α/θ power ratio also differed in a consistent way among the patient groups. Moreover, the main background frequency and the α/θ power ratio correlated significantly with functional and cognitive scores. Longitudinally, change in these parameters also showed significant correlation with the change in clinical and cognitive scores.

Conclusions: Our findings support the use of quantitative EEG to follow the progression of prion disease, with potential to help evaluate the treatment effects in future clinical-trials.

Figure 1

Location and grouping of electrodes.

Figure 2

Comparison of EEG parameters between healthy participants and patients with prion disease on the five-electrode groups. Error bars indicate the SEM. *p<0.0025, **p<0.0001. FL, left frontal; FR, right frontal; TL, left temporal; TR, right temporal electrode group; Z, central.

Figure 3

Comparison of EEG parameters among patients with asymptomatic or symptomatic IPD and sCJD on the five-electrode groups. Error bars indicate the SEM. *p<0.0025, **p<0.0001. FL, left frontal; FR, right frontal; IPD, inherited prion disease; sCJD, sporadic Creutzfeldt-Jakob disease; TL, left temporal; TR, right temporal electrode group; Z, central.

Figure 4

Correlation between the main background frequency and the MRC Scale (A)/ Mini Mental State Examination (MMSE) (B) scores for the symptomatic patients (sIPD and sCJD) with the 95% CI on the right frontal electrode group. FR, right frontal.

Figure 5

Correlation between the change in main background frequency and the change in MRC Scale (A)/Mini Mental State Examination (MMSE) (B) scores over time for the symptomatic patients (sIPD and sCJD) with the 95% CI on the right frontal electrode group. FR, right frontal.