Morphometric changes in the cochlear nucleus in patients who had undergone cochlear implantation for bilateral profound deafness¹

Abstract

We have investigated the morphometric changes in the cochlear nucleus of patients who had undergone cochlear implantation following profound deafness. The brain stems of 11 adult patients who had undergone implantation and four non-implanted control cases with varying degrees of hearing loss were studied. The volumes of the ventral cochlear nucleus (VCN) and dorsal cochlear nucleus (DCN), and the maximal cross-sectional area and densities of cell bodies in the anterior ventral cochlear nucleus (AVCN) were measured bilaterally by light microscopy assisted by the Neurolucida 2000 image analysis system. In addition, the density of synapses on cells of the AVCN were estimated using immunostaining for the synaptosome-associated protein (SNAP-25) by light microscopy. There was no significant difference in volumes of VCN and DCN, maximal cross-sectional area and density of cell bodies of the AVCN, and SNAP-25 immunostaining between the cochlear nucleus ipsilateral and contralateral to cochlear implantation. In addition, there was no significant correlation between these morphometric parameters and clinical performance. Peripheral deafness seems to reduce the size of neurons in the AVCN in that the maximum diameter of cell bodies was greater in the ear with better hearing preoperatively (chi-square test P<0.05). However, electrical stimulation provided by the cochlear implantation did not alter these morphometric changes in adult cochlear implant patients.

Introduction

Factors other than peripheral auditory neural integrity may affect performance with multichannel cochlear implants. Thus, six preoperative measures accounted for 61% of the inter-subject variability in NU6 (Northwestern University Auditory Test No.6) word recognition, and only two of these six measures could be attributed to the remaining spiral ganglion cell counts (Gantz et al., 1993). Likewise, in a composite analysis of data from 808 cochlear implant subjects, the four factors thought to be related to residual spiral ganglion cell count accounted for only 21% of the variance in the speech perception of the subject(Blamey et al., 1996). In addition, in a histopathologic study of seven patients who had cochlear implants, there was an apparent negative correlation between total spiral ganglion cell count and speech comprehension during life (Nadol et al., 2001). Thus, the degree of integrity of the central auditory pathway and other factors may have a significant influence on the performance using cochlear implants.

All afferent auditory neurons synapse in the cochlear nucleus, which is the most peripheral of the central auditory nuclei. In animal studies, significant changes in volume of the cochlear nucleus, cross-sectional areas of neural cell bodies, and density of neurons has been observed following peripheral deafening(Hultcrantz et al., 1991, Niparko and Finger, 1997, Lesperance et al., 1995, Hardie and Shepherd, 1999, Lustig et al., 1994, Willott et al., 1994). Thus, the total volume of the cochlear nucleus may be reduced by 46% in neonatally deafened cats compared to normal (Hardie and Shepherd, 1999). Similarly, the size of spherical cells in the anterior ventral cochlear nucleus (AVCN) may be reduced by as much as 38% in the deaf Dalmatian dog compared to age-matched controls (Niparko and Finger, 1997). Also, in the guinea pig following unilateral neomycin deafening, the average cross-sectional area of neuronal somata in the rostral AVCN was 22% smaller on the lesioned side compared to the normal hearing side (Lesperance et al., 1995). The effect of unilateral stimulation on subsequent neural atrophy in the cochlear nucleus is unclear (Hultcrantz et al., 1991, Niparko and Finger, 1997, Lesperance et al., 1995, Hardie and Shepherd, 1999, Lustig et al., 1994, Willott et al., 1994, Matsushima et al., 1991). In the cat, although neonatal deafening does result in a decrease in the volume of the cochlear nucleus and also the cross-sectional area of spherical cells, no significant difference between the stimulated and unstimulated side was found (Hultcrantz et al., 1991). On the other hand, following electrical stimulation in deafened kittens, the area of cell bodies in the AVCN on the stimulated side was significantly larger than corresponding controls on the unstimulated side (Matsushima et al., 1991). However, to date the findings in the human auditory central nervous system following cochlear implantation has been limited to six individuals and no significant changes have been seen in the cochlear nucleus attributable to stimulation (Moore et al., 1997, Terr et al., 1988, Clark et al., 1988). In this study, we evaluated the effects of deafness and electrical stimulation on cells of the cochlear nucleus in 11 patients who had undergone cochlear implantation by comparing the volumes of the ventral cochlear nucleus (VCN) and dorsal cochlear nucleus (DCN) and the density and size of cell bodies in the AVCN on the stimulated and non-stimulated sides. In addition, four patients without cochlear implants suffering varying degrees of hearing loss, served as non-implant controls. Finally, the density of synapses in the AVCN where spherical bushy cells (SBCs) are abundant, were evaluated. Large auditory nerve terminals, the so-called endbulbs of Held, synapse on the somata of SBCs, which demonstrate electrophysiologic responses identical to those of type I auditory nerve fibers. SNAP-25 (synaptosome-associated protein 25) immunostaining was used to evaluate the density of perisomatic synapses in the AVCN. SNAP-25 is a synaptosomal associated protein of 25 kDa (Hodel, 1998) and belongs to a family of conserved proteins thought to be essential for exocytosis and may control neurotransmitter release by playing a role in both the docking and fusing of membranes.