CLN2 is a rapidly progressive neurodegenerative disease caused by lysosomal TPP1 enzyme deficiency. This enzyme deficiency is ubiquitous throughout the body. However, the central nervous system and retina are predominantly affected. One sensory pathway of the central nervous system that has not been well studied and which subjectively appears to function well even in severely ill patients is the auditory pathway.
In order to study whether this pathway is affected by the disease, we recorded brainstem auditory evoked potentials (BAEP) in CLN2 patients at different stages of the disease receiving enzyme replacement therapy (ICV-ERT) with cerliponase alfa.
BEAP is a non-invasive electrophysiological method used to assess the functional integrity of the auditory pathway from distal auditori nerv (I), proximal auditory nerve (II), cochlear nucleus (III), superior olivary complex (IV) up to Lemniscus lateralis (V). We recorded 63 BEAPs in 57 CLN2 patients. The age of the patients at recording ranged from 13.5 to 198.3 months, with a median age of 86.9 months. The recorded responses were analyzed for presence, latency (interpeak-differences), and amplitude of each wave (I, III, V).
We observed interpeak-differences in ranges of 1.33-3.08 ms (I-III), 1.02-2.42 (III-V) and 3.13-4.91 (I-V). Comparison with age matched reference values (Sanfis et al. 2022) showed higher values for the I-V interpeak difference in 49 of 55 BEAPs in both ears. Moreover, these interpeak differences I-V were + 2σ above the upper reference range (3.36-4.0 (0.25)) in 10 BEAPs. These results represent a prolongation in the conduction velocity along the entire central auditory pathway.
The abnormalities found in this pilot project may indicate that the disease could affect the processing of auditory signals. Similar results have already been described in other neurodegenerative diseases such as Parkinson disease. Further studies must be conducted to investigate the pathogenic mechanism in the hearing system.