Anders Kinnefors

The human spiral ganglion: new insights into ultrastructure, survival rate and implications for cochlear implants.

This study was based on high-resolution SEM assessment of freshly fixed, normal-hearing, human inner ear tissue. In addition, semiquantitative observations were made in long-term deafened temporal bone material, focusing on the spiral ganglia and nerve projections, and a detailed study of the fine bone structure in macerated tissues was performed. Our main findings detail the presence of extensive bony fenestrae surrounding the nerve elements, permitting a relatively free flow of perilymph to modiolar structures. The clustering of the spiral ganglion cells in Rosenthal’s canal and the detailed and intricate course of postganglionic axons are described. The close proximity of fibers to cell soma is demonstrated by impression in cell surfaces, and presence of small microvilli-like structures at the contact regions, anchoring nerve fibers to the cell wall. Extensive fenestrae and the presence of a fragile network of endosteal bony structures at the surfaces guiding nerve fibers are described in detail for the first time. This unique freshly prepared human material offers the opportunity for a detailed ultrastructural study not previously possible on postmortem fixed material and more accurate information to model electrostimulation of the human auditory nerve through a cochlear implant. On the basis of this study, we suggest that the concentration and high density of spiral ganglion cells, and the close physical interaction between neural elements, may explain the slow retrograde degeneration found in humans after loss of peripheral receptors. Moreover, the fragile bony columns connecting the spiral canal with the osseous spiral lamina may be a potential site for trauma in (perimodiolar) electrode positioning.

Human cochlea: anatomical characteristics and their relevance for cochlear implantation.

This is a review of the anatomical characteristics of human cochlea and the importance of variations in this anatomy to the process of cochlear implantation (CI). Studies of the human cochlea are essential to better comprehend the physiology and pathology of mans hearing. The human cochlea is difficult to explore due to its vulnerability and bordering capsule. Inner ear tissue undergoes quick autolytic changes making investigations of autopsy material difficult, even though excellent results have been presented over time. Important issues today are novel inner ear therapies including CI and new approaches for inner ear pharmacological treatments. Inner ear surgery is now a reality, and technical advancements in the design of electrode arrays and surgical approaches allow preservation of remaining structure/function in most cases. Surgeons should aim to conserve cochlear structures for future potential stem cell and gene therapies. Renewal interest of round window approaches necessitates further acquaintance of this complex anatomy and its variations. Rough cochleostomy drilling at the intricate “hook” region can generate intracochlear bone‐dust‐inducing fibrosis and new bone formation, which could negatively influence auditory nerve responses at a later time point. Here, we present macro‐ and microanatomic investigations of the human cochlea viewing the extensive anatomic variations that influence electrode insertion. In addition, electron microscopic (TEM and SEM) and immunohistochemical results, based on specimens removed at surgeries for life‐threatening petroclival meningioma and some well‐preserved postmortal tissues, are displayed. These give us new information about structure as well as protein and molecular expression in man. Our aim was not to formulate a complete description of the complex human anatomy but to focus on aspects clinically relevant for electric stimulation, predominantly, the sensory targets, and how surgical atraumaticity best could be reached. Anat Rec, 2012.

Unique expression of connexins in the human cochlea

Mutations in the genes GJB2 and GJB6, which encode the proteins Connexin 26 (Cx26) and Connexin 30 (Cx30), have been linked to nonsyndromic prelingual deafness in humans. These proteins may form so-called gap junctions (GJ) or transcellular pathways between cells. The pathogenesis of deafness due to GJ Connexin mutations remains unclear partly because examinations performed in the human ear are infrequent. Here we analysed the expression and distribution of Cx26 and Cx30 in five fresh normal human cochleae taken out at occasional surgery. Immunohistochemistry including confocal microscopy in decalcified specimen showed that these proteins are widely expressed in the human cochlea. In the lateral wall there was strong antibody co-labeling for Cx26 and Cx30 that support the existence of channels comprising heteromeric Cx26/Cx30 connexons. In the organ of Corti there were some co-labeling in the supporting cell area including mainly the Claudius cells and Deiter cells of these two Cxs, apart from isolated Cx26 and Cx30 labeling in the same area, suggestive of both homomeric/homotypic pattern and hybrid pattern (heteromeric or heterotypic). Cx30, Cx26 and Connexin 36 (Cx36) immunoreactivity was also associated with spiral ganglion type I neurons, the latter being a gap junction protein specific to neurons. Gap-junction-based electrical synapses are not known to occur in mammalian auditory system other than in bats where they may play a role for fast electrical nerve transmission useful for echolocation. Their potential role in the processing of human auditory nerve signaling as well as non-GJ roles of the connexins in human cochlea is discussed.

Synapses on human spiral ganglion cells : a transmission electron microscopy and immunohistochemical study

A transmission electron microscopy (TEM) study and synaptophysin immunoreactivity analysis of neurons in the human spiral ganglion was performed with particular emphasis on the demonstration of synapses. The study was based on surgical biopsy material obtained during transcochlear meningioma surgery. Vesiculated nerve endings of unmyelinated nerve fibers occurred frequently on the small ganglion cells at all levels. The nerve terminals exhibited abundant clear synaptic vesicles but also dense-core vesicles. Multisynaptic contact sites were also seen with fibers of the intraganglionic spiral bundle (IGSB). Complex associations of synapses could be demonstrated, including several synaptic terminals in conjunction with contact sites or an adherent type of junctions on large ganglion cells. These contact sites exhibited membrane densities which were symmetric or asymmetric, changed their polarity recurrently over their extension from one cell to the other and back and lacked clear synaptic vesicles. This suggests the existence of connections between efferents, belonging to the olivocochlear bundle, and both small and large ganglion cells. Thus, both the inner and outer hair cell system may be under the influence of efferent innervation in the human spiral ganglion. The morphology and course of synaptophysin-positive nerve fibers indicated that synaptic contacts within the spiral ganglion, as observed under the electron microscope, may be abundant. These results indicate that complex neural processing may occur at the level of the spiral ganglion in man.

“Endolymphatic Sacitis” in a Case of Active Meniere's Disease An Ultrastructural Histopathologic Investigation

An ultrastructural analysis of an entire intraosseous endolymphatic sac (ES) from a patient with active, well-documented Menieres disease was performed for the first time. The results were compared with those obtained from ES biopsy material from patients with acoustic neuromas. The ES was small in size and showed signs of focal inflammation with intraepithelial invasion by mononuclear cells. At these places the normal fine structure, including the vascular anatomy, was altered. The possible relationship between these changes and Menieres disease is discussed.

Tinnitus and Translabyrinthine Acoustic Neuroma Surgery

The purpose of this investigation was to study the effects of translabyrinthine acoustic neuroma surgery on tinnitus in a consecutive sample of patients operated on between 1988 and 1994 in Uppsala (Sweden). A postal questionnaire was returned by 141 patients, yielding a 90% response rate without reminder. The results showed that tinnitus was experienced by 70% of the patients before surgery and 60% after surgery. In general, low degrees of tinnitus distress were found, which was confirmed by the questionnaire results. Ratings of tinnitus distress after surgery, using the Klockhoff and Lindblom grading system, showed that 48% had tinnitus of grade I, 46% of grade II, and 6% of grade III. Pre- and postsurgery grading of distress did not change significantly. There was a 35% risk for developing tinnitus when no preoperative tinnitus was present and a 15% chance that tinnitus disappears when present preoperatively.

Expression of peripherin in human cochlea

The organ of Corti contains two different types of auditory receptors; the inner (IHCs) and outer (OHCs) hair cells. This dualism is further represented in their innervation, IHCs being innervated by type I neurons, and OHCs by type II neurons (in man, named small ganglion cells). Two efferent systems are also present. Here, we have analyzed the expression of the 57-kDa neuron-specific intermediate filament protein peripherin (PP) in human cochlea. In the human organ of Corti, PP seems to be specifically expressed in OHC afferents. Small or type II spiral ganglion cell bodies also intensely express PP. Thus, PP can be used as a marker for the characterization of the innervation of the OHC system in man.

Nerve fibre interaction with large ganglion cells in the human spiral ganglion : A TEM study

A TEM study was performed on freshly fixed human spiral ganglions (HSG) biopsied during skull base surgery. Well preserved tissue specimens were obtained for ultrastructural analysis. The investigation revealed that nerve fibres frequently form contacts with the large ganglion cells (type I cells). In the areas of contact, membrane specializations occurred, consisting of symmetric or asymmetric densities often alternating from one cell to the other with a reduced intercellular distance (approximately 10 nm). High power TEM showed the intercellular cleft to contain an extra dense line resulting in a pentalaminar structure. The dense line appeared on the side of the membrane protein concentration. Protein densities jutted into the cytoplasm along the intracellular face spreading into a diffuse cytoplasmic web physically related to accumulating mitochondria. This indicated a concentration of oxygen-dependent metabolic activity in these regions. It is believed that the nerve junctions are involved in electric transmission between type I ganglion cells. The neural junctions were morphologically different from synaptic contacts between small human ganglion cells (type II cells) and nerve fibres which have been suspected of sharing the olivocochlear bundle as their origin.

Surgical treatment of adult cholesteatoma: long-term follow-up using total reconstruction procedure without staging

Abstract Conclusions: A total of 330 cases of adult cholesteatoma were operated with canal-wall down (CWD) and total reconstruction procedure (TRP) without staging. Independent of preoperative middle ear conditions, cholesteatoma extent and localization, long-term improvement of hearing with a low incidence of residual and recurrent disease were achieved. Objectives: To evaluate long-term surgical and hearing results using a well-defined surgical technique without staging in adult cholesteatoma. Methods: The same CWD surgical technique, including obliteration of the mastoid cavity, reconstruction of the canal wall, and ossiculoplasty with autologous bone, was used by three senior surgeons (1982–2004). Preoperative and postoperative pure tone average (PTA) for air conduction (AC), bone conduction (BC), and air–bone gap (ABG) were assessed and compared 1, 3, and 6 years after surgery. Various prognostic factors with potential influence on long-term hearing outcome were evaluated. Results: Recurrence of AC occurred in 10%, residual disease in 3%. Six years after surgery all patients except one had a dry ear and over 92% of all cases were water resistant. Three patients developed complete deafness. Long-lasting improvement and/or preservation of hearing, with maintenance of PTA-ABG closure in 68% of all cases within 20 dB, were obtained. Sixty-four (19%) ossicular revisions were performed.

Expression of TrkB and BDNF in human cochlea—an immunohistochemical study

Surgical human cochlear specimens were obtained during the removal of large posterior cranial fossa meningioma by a transcochlear approach in which the cochlea was removed for maximal exposure of the tumor and protection of important structures, such as the brainstem, cranial nerves, and pivotal blood vessels. The cochlear tissue was fixed and cryo-sectioned for tyrosine kinase receptor B (TrkB) and brain-derived neurotrophic factor (BDNF) immunohistochemistry. TrkB receptor protein was expressed in both neuronal somata and the processes of human spiral ganglion neurons (SGNs). In the human organ of Corti, TrkB immunoreactivity was mainly present in nerve fibers underneath outer hair cells. BDNF expression was found neither in the organ of Corti nor in the spiral ganglion of human cochlea. For antibody specificity and for control and comparative purposes, TrkB immunocytochemistry was performed in primary cultures of cochlear neuron/glia from adult guinea pig. Confocal laser scanning microscopy showed that TrkB was homogeneously distributed in the cytoplasm of both neuronal somata and axons. Knowledge of the expression of TrkB receptor in human cochlea should help to determine the target structures for neuron preservation in hearing-impaired patients. Our results indicate that the regeneration of SGNs under pathological conditions can be enhanced with BDNF/TrkB-based pharmaceutical or genetic strategies.