Niklas Danckwardt-Lillieström

Ultrastructural Evidence of a Merocrine Secretion in the Human Endolymphatic SAC

The results of a light and transmission electron microscopic analysis of an endolymphatic sac (ES) from a patient suffering from episodic vertigo, tinnitus, and hearing loss are presented. A biopsy of the intraosseous portion of the ES was obtained during a translabyrinthine approach to section the vestibular nerve in the internal acoustic meatus. The material consisted mainly of tubular epithelial structures filled with heavily stained material. Pathologically dilated and degranulated rough endoplasmic reticuli and disaggregation of polyribosomes with accumulation of solitary ribosomes in the cytosol and endoplasmic reticulum suggested a disturbed epithelial cell protein synthesis. Ultrastructural evidence of an increased merocrine secretion of glycoprotein conjugates into the ES was noted. This made it possible to analyze the presumed intracellular secretory pathways. An increased number of intraepithelial lymphocytes and monocytes was observed. Since the inner ear had been subjected to surgical intervention before the vestibular nerve section, no conclusions can be drawn as to whether the patients symptoms were related to the disturbed protein metabolism and hypersecretion of glycoprotein conjugates into the ES. The findings support earlier experimental results that indicate that the ES has not only a resorptive function but also a secretory one.

“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.

Surgical Treatment of Patients With Facial Neuromas : A Report of 26 Consecutive Operations

Objective: To analyze surgical treatment and outcome in patients with facial neuromas at a tertiary referral hospital. Study Design: A chart review of 26 patients treated between 1971 and 2006, with questionnaire follow-up ranging from 2 to 19 years. All patients except one were operated with radical tumor removal approaches. Results: Approximately 54% of the patients presented with symptoms related to the VIIth cranial nerve (facial palsy and facial spasm), 58% with symptoms related to the VIIIth cranial nerve (hearing deficit, tinnitus, and vertigo), and 8% related to the Vth cranial nerve (facial pain and facial sensory deficit). Approximately 39% presented with no facial symptoms. Twenty-one patients received a facial nerve graft from the greater auricular nerve or the sural nerve; 1 patient had an accessory-facial anastomosis. One patient had a subtotal tumor removal preserving the facial nerve. Three patients were not grafted. Most tumors (88%) affect the geniculate ganglion. Approximately 82% of the grafted patients regained a House-Brackmann facial nerve function (HB) grade III; 14% regained HB grades IV to V. No serious morbidity or mortality was reported. No recurrences have been reported where a total tumor removal was performed. Conclusion: Surgical removal of facial neuroma is a safe procedure with a low complication rate and a low recurrence rate. First symptoms are diverse and are predominantly derived from the facial and vestibulocochlear nerve. Facial nerve grafting is reliable, giving the patient an acceptable facial nerve function (HB III).

Ultrastructural analysis of 20 intraosseous endolymphatic sacs from patients with cerebello-pontine angle tumours: A surgically obtained control material for histopathological studies

OBJECTIVE The purpose of this work was to collect a surgically obtained, freshly fixed material of the human intraosseous endolymphatic sac. This biopsy material was used to describe the normal ultrastructure as well as to serve as a control material for histopathological studies on Ménières disease in particular. METHOD The specimens, obtained during surgery for cerebello-pontine angle tumours, were fixed by immersion and then prepared by routine methods for transmission electron microscopy. The ultrastructural analysis was focused on intraluminal content, epithelial cell layer, subepithelial space, and morphological signs of immunological activity. The ultrastructure was analysed in relation to inner ear sensory function, tumour diagnosis, and patients age and sex. RESULTS As it was possible to obtain numerous specimens with an intact bony shell, the intraluminal substance could be analysed. Two separate epithelial cell types are described: one less abundant, often lighter and mitochondria-rich cell type; the other, often darker, epithelial cell with fever mitochondrias. Some of the latter cell types showed signs of active secretion. The subepithelial space was characterized by loose connective tissue adjacent to the epithelial lining, being more dense toward the bone. Elastic fibres were seen surrounding the entire endolymphatic sac. Macrophages in the intraluminal space and lymphocytes in the epithelial and subepithelial layers are described. No distinct morphology correlating to inner ear sensory function, tumour diagnosis, or patients age and sex was revealed. CONCLUSIONS This study confirms previously described, extensive variations in form and structure of the human endolymphatic sac. Various factors, such as surgical trauma, previous treatment, and processing method, can affect the ultrastructure and must be taken into consideration. The specimens described in this work appear to constitute a good control material for histopathological study of the human endolymphatic sac. It is still necessary to obtain large control materials such as this, as surgical specimens from patients with Ménières disease are uncommon.

Localization of Hyaluronan in the Human Endolymphatic Sac: A Study Using the Affinity Hyaluronan Binding Protein

This study was undertaken with the aim of localizing hyaluronan (hyaluronic acid, HYA) in tissue sections of the human endolymphatic sac by use of a hyaluronan-binding affinity protein and the avidin-biotin/peroxidase staining procedure. Five human endolymphatic sacs were removed during surgery for acoustic neuroma. After microwave-aided fixation and decalcification, paraffin-embedded sections were prepared by routine histological methods. HYA was detected in some of the intraluminal substance as well as in parts of the epithelial lining, mainly in the rugose portions of the endolymphatic sac. HYA was observed intracellularly in epithelial cells. It was also found in the subepithelial tissue near the epithelia and close to the bony aqueduct. The distribution of HYA was uneven at all locations. The finding of HYA within the human endolymphatic sac may imply that this substance has important functions in the control of inner ear fluid homeostasis.

Lymphocyte-macrophage activity in the human endolymphatic sac.

The human endolymphatic sac was analysed electron microscopically in patients undergoing acoustic Schwannoma surgery or vestibular nerve section. In addition, endolymphatic sacs from cadavers were analysed light microscopically. The results show that the human sac is endowed with a variable number of leucocytes and that there is a continuous recirculation of immuno-competent cells in this area of the inner ear that may be of importance for clearance of the inner ear from foreign substances and microorganisms derived from nearby located infection-prone areas. The possibility in Menieres disease of a disturbed immunological activity in the sac is discussed.

Non-echo planar diffusion-weighted MRI increases follow-up accuracy after one-step step canal wall-down obliteration surgery for cholesteatoma

Abstract Conclusion: Non-echo planar (non-EPI) diffusion-weighted (DW) magnetic resonance imaging (MRI) increases the number of detected cholesteatoma after one-step canal wall-down (CWD) obliteration surgery for cholesteatoma compared with clinical evaluation alone. Objective: To evaluate the use of DW-MRI for detection of cholesteatoma after surgical treatment using a CWD obliteration technique. Methods: Thirty-eight adult patients (41 ears) treated with an identical one-step CWD obliteration surgical technique were included in a prospective and blinded study. All patients were investigated with non-EPI and EPI DW-MRI 1–9 months after the clinical examination. Follow-up time after primary surgery varied between 10 and 234 months. DW-MRI was assessed by two neuroradiologists and compared with clinical results. Inter-rater agreement was calculated. Positive non-EPI DW-MRI cases underwent revision surgery within 18–159 days after imaging. Results: Seven of 41 cases were evaluated as positive for cholesteatoma on non-EPI DW-MRI. Since one patient refused surgery six of these seven cases underwent surgical revision and all were verified. There was agreement between clinical and non-EPI findings in five of eight cases. EPI findings correlated poorly with non-EPI and clinical findings. Inter-rater agreement (Cohens kappa) was 0.91 for non-EPI DW-MRI (p < 0.001) and –0.062 for EPI DW-MRI (p = 0.43)

A Technique to Obtain and Process Surgical Specimens of the Human Vestibular Aqueduct for Histopathological Studies of the Endolymphatic Duct and Sac

The endolymphatic sac (ES) may play a crucial role in the pathophysiology of Ménières disease. This paper presents a technique to obtain and process fresh human specimens of the endolymphatic duct (ED) and the presumably more active intraosseous portion of the ES obtained at surgery. The specimens are preserved with an intact bony shell around the ED and the intraosseous ES. This allows ultrastructural histopathological evaluation of the intraluminal contents, the epithelium and the subepithelial tissue as well as the mutual relationships of these structures. Various factors influencing ES ultrastructure are discussed. The results obtained from this method may increase our understanding of the possible role of the ES in the etiology of different inner ear disorders.

A Randomised, Double Blind Trial of N-Acetylcysteine for Hearing Protection during Stapes Surgery

Background Otosclerosis is a disorder that impairs middle ear function, leading to conductive hearing loss. Surgical treatment results in large improvement of hearing at low sound frequencies, but high-frequency hearing often suffers. A likely reason for this is that inner ear sensory cells are damaged by surgical trauma and loud sounds generated during the operation. Animal studies have shown that antioxidants such as N-Acetylcysteine can protect the inner ear from noise, surgical trauma, and some ototoxic substances, but it is not known if this works in humans. This trial was performed to determine whether antioxidants improve surgical results at high frequencies. Methods We performed a randomized, double-blind and placebo-controlled parallel group clinical trial at three Swedish university clinics. Using block-stratified randomization, 156 adult patients undergoing stapedotomy were assigned to intravenous N-Acetylcysteine (150 mg/kg body weight) or matching placebo (1:1 ratio), starting one hour before surgery. The primary outcome was the hearing threshold at 6 and 8 kHz; secondary outcomes included the severity of tinnitus and vertigo. Findings One year after surgery, high-frequency hearing had improved 2.7 ± 3.8 dB in the placebo group (67 patients analysed) and 2.4 ± 3.7 dB in the treated group (72 patients; means ± 95% confidence interval, p = 0.54; linear mixed model). Surgery improved tinnitus, but there was no significant intergroup difference. Post-operative balance disturbance was common but improved during the first year, without significant difference between groups. Four patients receiving N-Acetylcysteine experienced mild side effects such as nausea and vomiting. Conclusions N-Acetylcysteine has no effect on hearing thresholds, tinnitus, or balance disturbance after stapedotomy. Trial Registration ClinicalTrials.gov NCT00525551

High-frequency hearing, tinnitus, and patient satisfaction with stapedotomy: A randomized prospective study.

Otosclerosis is a common disorder that leads to conductive hearing loss. Most patients with otosclerosis also have tinnitus, and surgical treatment is known to improve hearing as well as tinnitus. Some patients however experience worsening of tinnitus after the operation, but there are no known factors that allow surgeons to predict who will be at risk. In this prospective observational study on 133 patients undergoing stapedotomy, we show that postoperative air conduction thresholds at very high stimulus frequencies predict improvement of tinnitus, as assessed with proportional odds logistic regression models. Young patients were significantly more likely to experience reduction of tinnitus and patients whose tinnitus became better were also more satisfied with the outcome of the operation. These findings have practical importance for patients and their surgeons. Young patients can be advised that surgery is likely to be beneficial for their tinnitus, but a less positive message should be conveyed to older patients.