Brainstem auditory-evoked potentials in experimental scrapie infected sheep

Scrapie is a fatal neurodegenerative disease of sheep and goats belonging to the group of transmissible spongiform encephalopathies (TSEs). These disorders are characterized by the progressive accumulation in the central nervous system of the pathological isoform (PrPSc) of a normal host protein (PrPc). The aim of this study was to describe the alterations of brainstem auditory-evoked potentials (BAEPs) in sheep experimentally challenged with scrapie. Five Sarda breed sheep with ages ranging from 9 to 10 months and genotypes ARR/ARQ, ARH/AHQ and ARR/AHQ were challenged intracerebral (i.c.) with scrapie. All subjects were examined on a regular basis and succumbed to the disease 29-41 months after inoculation. Diagnosis was confirmed by detection of PrPSc at the obex by Western blotting. Ten healthy Sarda breed sheep of similar ages were also included in the study as normal controls. BAEPs were performed in scrapie infected and in normal group with the same methodologies. Tests were recorded in the preclinical, 17 months postinfection, and in the clinical period, 27 months postinfection. Absolute amplitudes of the waves and relative interpeak latencies (IPL) were calculated. Data from infected group and from control group were compared using unpaired, two-tailed student's t test. Amplitudes of I wave were significantly reduced (P = 0.0022) 17 months postinfection compared to control group. Amplitudes of waves II, III and V didn’t differ significantly. IPL I-III in infected group weren’t significantly different from normal group, while IPL III-V were significantly prolonged (P = 0.0248) in infected group. The tests performed 27 months postinfection showed significant reductions of amplitudes of wave I (P < 0,0001) and II (P = 0.0373) and not significant differences of amplitudes of waves III and V. IPL I-III (P = 0.0075) and IPL III-V (P = 0.0059) were significantly prolonged in experimentally infected group compared to control group. These findings indicate the presence of alterations in BAEPs waveform in i.c. scrapie infected sheep. Reductions of wave I and II amplitudes and prolongation of IPL were present in clinically affected subjects. Interestingly, statistically significant differences in BAEPs waveforms were present in infected sheep also in the preclinical period. Further studies including more subjects, other genotypes, and sheep infected by oral route are needed to better define patterns of BAEPs abnormalities. BAEPs testing may represent a sensitive tool in both diagnosis and monitoring of scrapie.