Polarized Secretion of APRIL by the Tonsil Epithelium Upon Toll-Like Receptor Stimulation.

In mucosa such as tonsil, antibody-producing plasmocytes (PCs) lie in sub-epithelium space, which is thought to provide a suitable environment for their survival. A proliferation inducing ligand (APRIL) is one key survival factor for PCs present in this area. According to in situ staining, apical epithelial cells produced APRIL, and the secreted product had to migrate all through the stratified surface epithelium to reach basal cells. A similar process also occurred in the less-organized crypt epithelium. Tonsil epithelial cells captured secreted APRIL, thanks to their surface expression of the APRIL coreceptor, either syndecan-1 or -4 depending on their differentiation stage. In the most basal epithelial cells, secreted APRIL accumulated inside secretory lamp-1+ vesicles in a polarized manner, facing the sub-epithelium. The tonsil epithelium upregulated APRIL production by apical cells and secretion by basal cells upon Toll-like receptor stimulation. Furthermore, LPS-stimulated epithelial cells sustained in vitro PC survival in a secreted APRIL-dependent manner. Taken together, our study shows that the tonsil epithelium responds to pathogen sensing by a polarized secretion of APRIL in the sub-epithelial space, wherein PCs reside.

Drafting a Surgical Procedure Using a Computational Anatomy Driven Approach for Precise, Robust, and Safe Vestibular Neuroprosthesis Placement-When One Size Does Not Fit All.

OBJECTIVE: To design and evaluate a new vestibular implant and surgical procedure that should reach correct electrode placement in 95% of patients in silico. DESIGN: Computational anatomy driven implant and surgery design study. SETTING: Tertiary referral center. PARTICIPANTS: The population comprised 81 patients that had undergone a CT scan of the Mastoid region in the Maastricht University Medical Center. The population was subdivided in a vestibular implant eligible group (28) and a control group (53) without known vestibular loss. INTERVENTIONS: Canal lengths and relationships between landmarks were calculated for every patient. The relationships in group-anatomy were used to model a fenestration site on all three semicircular canals. Each patient's simulated individual distance from the fenestration site to the ampulla was calculated and compared with the populations average to determine if placement would be successful. MAIN OUTCOME MEASURES: Lengths of the semicircular canals, distances from fenestration site to ampulla (intralabyrinthine electrode length), and rate of successful electrode placement (robustness). RESULTS: The canal lengths for the lateral, posterior, and superior canal were respectively 12.1 mm ±â€Š1.07, 18.8 mm ±â€Š1.62, and 17.5 mm ±â€Š1.23, the distances from electrode fenestration site to the ampulla were respectively 3.73 mm ±â€Š0.53, 9.02 mm ±â€Š0.90, and 5.31 mm ±â€Š0.73 and electrode insertions were successful for each respective semicircular canal in 92.6%, 66.7%, and 86.4% of insertions in silico. The implant electrode was subsequently revised to include two more electrodes per lead, resulting in a robustness of 100%. CONCLUSIONS: The computational anatomy approach can be used to design and test surgical procedures. With small changes in electrode design, the proposed surgical procedure's target robustness was reached.

Palinopsia Following Acute Unilateral Partial Vestibular Deafferentation: A Case Report.

Palinopsia is defined as the persistence or reappearance of images after cessation of the visual stimulus. One patient presented episodes of palinopsia after the functional loss of the 3 semicircular canals of the right ear while the otolithic function was preserved. None of classical causes was identified in this patient, intoxications, brain tumors, migraines, psychiatric disorders, etc. For a movement to be perceived as a single event, central processes of temporal integration are necessary to correct the shift between the rapid vestibular information, and the slow visual information. However, it has been shown on animal models that vestibular inputs are slower than normal in case of peripheral deafferentation limited to the canalar function with preservation of the otolithic function, which is the case in this patient. Therefore, we hypothesize that episodes of palinopsia he presents result from the fact that temporal integration processes do not take into account the slower than normal vestibular information due to the peripheral disorder and continue to slow it down. Thus, the patient keeps the visual image in memory until the late arrival of the vestibular information.

The Vestibular Implant: Hearing Preservation during Intralabyrinthine Electrode Insertion-A Case Report.

OBJECTIVE: The vestibular implant seems feasible as a clinically useful device in the near future. However, hearing preservation during intralabyrinthine implantation remains a challenge. It should be preserved to be able to treat patients with bilateral vestibulopathy and (partially) intact hearing. This case study investigated the feasibility of hearing preservation during the acute phase after electrode insertion in the semicircular canals. METHODS: A 40-year-old woman with normal hearing underwent a translabyrinthine approach for a vestibular schwannoma Koos Grade IV. Hearing was monitored using auditory brainstem response audiometry (ABR). ABR signals were recorded synchronously to video recordings of the surgery. Following the principles of soft surgery, a conventional dummy electrode was inserted in the lateral semicircular canal for several minutes and subsequently removed. The same procedure was then applied for the posterior canal. Finally, the labyrinthectomy was completed, and the schwannoma was removed. RESULTS: Surgery was performed without complications. No leakage of endolymph and no significant reduction of ABR response were observed during insertion and after removal of the electrodes from the semicircular canals, indicting no damage to the peripheral auditory function. The ABR response significantly changed when the semicircular canals were completely opened during the labyrinthectomy. This was indicated by a change in the morphology and latency of peak V of the ABR signal. CONCLUSION: Electrode insertion in the semicircular canals is possible without acutely damaging the peripheral auditory function measured with ABR, as shown in this proof-of-principle clinical investigation.

Ethical, anatomical and physiological issues in developing vestibular implants for human use.

Effort towards the development of a vestibular implant for human use are being made. This paper will summarize the first important steps conducted in Geneva towards this ambitious goal. Basically, we have faced three major issues. First, an ethical issue. While it was clear that such development would require the collaboration of human volunteers, it was also clear that stimulation of the vestibular system may produce periods of significant incomfort. We know today how to minimize (and potentially eliminate) this type of incomfort. The second issue was anatomical. The anatomical topology of the vestibular system is complex, and of potentially dangerous access (i.e. facial nerve damage). We choose not to place the electrodes inside the ampullae but close the vestibular nerve branches, to avoid any opening of the inner ear and limit the risk of hearing loss. Work on cadaver heads, confirmed by acute stimulations trials on patients undergoing ear surgery under local anesthesia, demonstrated that it is possible to stimulate selectively both the posterior and lateral ampullary nerves, and elicit the expected vertical and horizontal nystagmic responses. The third issue was physiological. One of the goal of a vestibular implant will be to produce smooth eye movements to stabilize gaze direction when the head is moving. Indeed, after restoring a baseline or "rest" activity in the vestibular pathways with steady-state electrical stimulation, we demonstrated that modulation of this stimulation is producing smooth eye movements. In conclusion, humans can adapt to electrical stimulation of the vestibular system without too much discomfort. Surgical access to the posterior and lateral ampullary nerves have been developed and, electrical stimulation of the vestibular system can be used to artificially elicit smooth eye movements of different speeds and directions, once the system is in adapted state. Therefore, the major prerequisites to develop a prototype vestibular implant for human use are fulfilled.

The modified ampullar approach for vestibular implant surgery: feasibility and its first application in a human with a long-term vestibular loss.

OBJECTIVE: To assess, for the first time in a human with a long-term vestibular loss, a modified approach to the ampullae and the feasibility of evoking a VOR by ampullar stimulation. MATERIALS AND METHODS: Peroperative stimulation of the ampullae, using the ampullar approach, was performed under full anesthesia during cochlear implantation in a 21-year-old female patient, who had experienced bilateral vestibular areflexia and sensorineural hearing loss for almost 20 years. RESULTS: The modified ampullar approach was performed successfully with as minimally invasive surgery as possible. Ampullar stimulation evoked eye movements containing vectors congruent with the stimulated canal. As expected, the preliminary electrophysiological data were influenced by the general anesthesia, which resulted in current spread and reduced maximum amplitudes of eye movement. Nevertheless, they confirm the feasibility of ampullar stimulation. CONCLUSION: The modified ampullar approach provides safe access to the ampullae using as minimally invasive surgery as possible. For the first time in a human with long-term bilateral vestibular areflexia, it is shown that the VOR can be evoked by ampullar stimulation, even when there has been no vestibular function for almost 20 years. This approach should be considered in vestibular surgery, as it provides safe access to one of the most favorable stimulus locations for development of a vestibular implant.

[Jugular and tympanic paragangliomas]. / Les paragangiomes jugulaires et tympaniques.

Jugular and tympanic paragangliomas are the most frequent tumors of the middle ear. They appear as a reddish, pulsatile, retrotympanic mass. Patients complain from hearing loss and pulsatile tinnitus. Tumors are most often benign. Secretory forms are rare. Angio-MRI and CT-scan are gold standard. MIBG or octreotid scintigraphies are helpful to rule out multiple lesions. The treatment consists in surgery alone, radiotherapy alone or association of both. Often, embolisation prior to surgery decreases hemorrhagic risks. Vital prognosis is good. The functional outcome is critical in extensive tumors.

APRIL secreted by neutrophils binds to heparan sulfate proteoglycans to create plasma cell niches in human mucosa.

The bone marrow constitutes a favorable environment for long-lived antibody-secreting plasma cells, providing blood-circulating antibody. Plasma cells are also present in mucosa-associated lymphoid tissue (MALT) to mediate local frontline immunity, but how plasma cell survival there is regulated is not known. Here we report that a proliferation-inducing ligand (APRIL) promoted survival of human upper and lower MALT plasma cells by upregulating expression of the antiapoptotic proteins bcl-2, bcl-xL, and mcl-1. The in situ localization of APRIL was consistent with such a prosurvival role in MALT. In upper MALT, tonsillar epithelium produced APRIL. Upon infection, APRIL production increased considerably when APRIL-secreting neutrophils recruited from the blood infiltrated the crypt epithelium. Heparan sulfate proteoglycans (HSPGs) retained secreted APRIL in the subepithelium of the infected zone to create APRIL-rich niches, wherein IgG-producing plasma cells accumulated. In lower MALT, neutrophils were the unique source of APRIL, giving rise to similar niches for IgA-producing plasmocytes in villi of lamina propria. Furthermore, we found that mucosal humoral immunity in APRIL-deficient mice is less persistent than in WT mice. Hence, production of APRIL by inflammation-recruited neutrophils may create plasma cell niches in MALT to sustain a local antibody production.

Intratympanic application of an antiviral agent for the treatment of Ménière's disease.

It has been suggested that Ménière's disease is part of a polyganglionitis in which symptoms result from the reactivation of neurotropic virus within the internal auditory canal, and that intratympanic applications of an antiviral agent might be an efficient therapy. In 2002, we performed a pilot study ending with encouraging results. Control of vertigo was achieved in 80% of the 17 patients included. We present here a prospective, double-blind study, with a 2-year follow-up, in 29 patients referred by ENT practitioners for a surgical treatment after failure of a medical therapy. The participation in the study was offered to patients prior to surgery. A solution of ganciclovir 50 mg/ml or of NaCl 9% was delivered for 10 consecutive days via a microwick inserted into the tympanic membrane in the direction of the round window or through a ventilation tube. One patient was withdrawn from the study immediately after the end of the injections. He could not complete the follow-up period, because of persisting vertigo. As he had received the placebo, he was then treated with the solution of ganciclovir. Symptoms persisted and he underwent a vestibular neurectomy. Among the remaining 28 patients, surgery could be postponed in 22 (81%). Surgery remained necessary to control vertigo in 3 patients from the group that received the antiviral agent, and in 3 from the control group. Using an analogical scale, patients of both groups indicated a similar improvement of their health immediately after the intratympanic injections. The scores obtained with a 36-item short-form health survey quality of life questionnaire and the Dizziness Handicap Inventory were also similar for both groups. In conclusion, most patients were improved after the intratympanic injections, but there was no obvious difference between the treated and control groups. The benefit might be due to the middle ear ventilation or reflect an improvement in the patients' emotional state.

Benign paroxysmal positional vertigo: a series of eight singular neurectomies.

CONCLUSION: The singular neurectomy as described by Gacek in 1974 is an efficient procedure to control symptoms in case of intractable benign paroxysmal positional vertigo (BPPV), with an acceptable risk of postoperative sensorineural hearing loss (SNHL). We postulate that this complication may not be a direct consequence of the surgical procedure but rather may be consecutive to the reactivation of the biological phenomenon that caused the BPPV. We also observed in one patient that BPPV may exist although no nystagmus can be elicited by provocative manoeuvres. OBJECTIVE: To report our experience of the surgery, and to analyse the rate and causes of complications. PATIENTS AND METHODS: The eight patients operated in the department between August 1997 and April 2006 were evaluated in June 2006. One had been operated because he had a typical history of BPPV, but no nystagmus could be elicited by the Hallpike's manoeuvre. RESULTS: All patients were free of vertigo and considered their quality of life improved. The Hallpike's manoeuvre was negative in all cases. A SNHL occurred in two patients, immediately after surgery in one and several months later in the second. The patient with a negative Hallpike's manoeuvre before surgery went back to work 3 weeks after surgery.

Benefits and costs of universal hearing screening programme.

Hearing loss affects 1-3 out of 1000 newborns. A programme of universal newborn hearing screening (UNHS) was implemented in our ENT department in February 2000. In 2001, the programme was extended to all the hospitals of the canton Geneva. The programme is based on the recording of transient evoked otoacoustic emissions (TEOAE) from all newborns. In addition, automated auditory brainstem responses (aABR) are recorded in high-risk neonates. In the report, we compare the mean age at which rehabilitation of hearing was undertaken during a 5-year period before and after the screening programme was instituted. We also identify some causes of delayed diagnosis and intervention and the pitfalls of universal hearing screening. The price of the UNHS programme is estimated at 26 Swiss francs (17 Euros; 21 US dollars) per infant screened, including the material required, the personal involved to run the programme, and the follow-up.

Partial withdrawal of deeply inserted cochlear electrodes: observations of two patients.

Three patients implanted in our department received the preformed Clarion S-Series cochlear implant with the electrode Positioning System (EPS). The EPS is a device designed to bring the electrode array closer to the modiolus and deeper into the cochlea. Two of these patients still complained because they were perceiving too low pitch sounds, and because of the presence of echoes and poor discrimination after 3 years of implant use and many tuning sessions. We hypothesized that the electrode array was too deeply inserted and could be stimulating overlapping populations of neurons in the low frequency range. The EPS was removed through a transcanal tympanotomy under local anesthesia and the array was pulled 2-3 mm out of the cochlea. The angle of electrode insertion into the cochlea and the patients' performances on consonant identification tests were evaluated before and after the removal surgery and over the long term, 3 years after the surgery. Immediately after the removal surgery the angle of insertion of the electrode array decreased from 720 degrees to 485 degrees in one case and from 675 degrees to 485 degrees in the other. Both patients reported subjective improvements after the removal which were confirmed by tests of performance at the long term by one of the patients. These observations show that (1) the electrode array can be moved without deterioration of performances even several years after being implanted; revision surgery may be beneficial in some cases, (2) neighboring electrodes might stimulate overlapping populations of neurons, inducing a deterioration of performances; for anatomical reasons, this is most likely to occur in the apex of the cochlea and (3) tuning of the external processor should be a customized procedure.

Patients' lives following stapedectomy complications.

Nowadays, it is widely accepted that patients must be informed about the risks associated with any type of surgical procedure. Usually, the information provided consists of quoting a list of risks and their probability of occurrence based on data from the literature, and, more appropriately, the figures reflecting the surgeon's personal experience. As a rule, such data are sufficient to hold up in court in the event of a lawsuit, but may be insufficient to help patients make the most appropriate choice. We report two cases that presented complications following stapedotomy. Both cases had a sensorineural hearing loss and a vestibular deficit. This paper aims at describing the important psychological and social consequences of these complications. The potential impact of such complications on the quality of life and the projects for the future of these young patients was predictable. In order to better assist patients in choosing amongst options, we have taken action and modified our approach in advising our patients eligible for stapedotomy procedures.

Transcanal approach to the singular nerve.

OBJECTIVES/HYPOTHESIS: Intractable benign paroxysmal positional vertigo is rare, and surgery is indicated in only a very small number of cases. Transcanal singular neurectomy is considered a difficult and risky procedure possibly leading to hearing loss and vertigo. The objective of this study was to evaluate the feasibility of the singular neurectomy through the external ear canal in an attempt to explain the contradictory results of previous reports of anatomists and of surgeons who abandoned the technique, considering that the singular neurectomy could not be reached via the external auditory canal without damaging the labyrinth. MATERIALS AND METHODS: Anatomical study on 100 halves of human heads in which the canal of the singular nerve (SN) was identified and opened at its extremities, the internal auditory canal and the ampulla of the posterior semicircular canal, via a posterior fossa approach. Next, the canal of the SN was dissected via the external auditory canal, at the floor of the round window (RW) niche. The relation of the SN canal to the ampulla of the posterior semicircular canal was evaluated. RESULTS: In 90 cases, the canal was transected medially to and away from the ampulla of the posterior semicircular canal, and in 8, at its emergence from the posterior ampullary recess. In these 98 cases, the RW membrane and the bony labyrinth were kept intact. In two cases, the canal of the SN could not be reached at the floor of the RW niche. CONCLUSION: Singular neurectomy is feasible via the external auditory canal, without damaging the RW membrane or the labyrinth in 98% of the cases. Because singular neurectomy is indicated in a very small number of cases, it is difficult to master this particular surgical procedure. This may explain why most surgeons abandoned the technique after a few attempts, followed by an unacceptable rate of sensorineural hearing loss.

Anatomic and functional long-term results of canal wall-down mastoidectomy.

The objective of this study was to evaluate, over the long-term, the anatomic and functional outcome of canal wall-down mastoidectomy performed for chronic otitis media with cholesteatoma and chronic otomastoiditis resistant to all conservative treatment. The study was made through a retrospective review of 338 cases of consecutive primary canal wall-down mastoidectomies performed between 1974 and 1998. Included were 259 cases with sufficient data. In all cases, functional reconstruction was performed at the same time as the mastoidectomy. Demographic and clinical data were collected from each file. From the clinical data, the surgical techniques, complications, the number of follow-up visits necessary to ensure cavity cleanliness, details of care provided over the period 1 to 24 years (mean, 7 years) after the operation, and audiometric data from admission and from the latest postoperative follow-up were retained. Canal wall-down mastoidectomies were followed up an average of 10 times during the first 6 months after operation, twice a year over the 6-year period following surgery, and less than twice a year beyond the 6-year period. Care was dispensed for meatal stenosis, scars, infections, polyps, and beads of cholesteatoma. Surgical revisions were performed because of residual or recurrent cholesteatoma in 6.1% of the cases, because of perforation of the tympanic membrane in 7.3% of the cases, and to improve hearing in 12.2% of the cases. At the last consultation, 1 to 24 years after surgery, cavities were found to be dry and self-cleaning in 95% of the cases, and still humid, with otorrhea, in 5% of the cases. Over the long-term, the hearing threshold remained unchanged in 41.3% of the cases. It was improved after surgery by 10 to 19 dB in 15.4% of the cases, by 20 to 29 dB in 11.5% of the cases, and by more than 29 dB in 3.8% of the cases. The hearing threshold was thus improved or at least remained unchanged in 72.0% of cases. Hearing losses occurred in 28% of the cases: by 10 to 19 dB in 11.9%, by 20 to 29 dB in 6.5%, and by more than 29 dB in 9.2% of the cases. A sensorineural hearing loss of more than 60 dB at all frequencies occurred immediately after the operation in 2 cases (0.7%). There was 1 case of facial paralysis (0.3%). Four patients (1.5%) complained of persistent vertigo. Canal wall-down mastoidectomy is an adequate treatment for chronic otitis with cholesteatoma or chronic otomastoiditis. The anatomic and functional results are satisfactory, and the rate of complications is acceptably low. A tympanoplasty can be performed simultaneously. Thus, for the large majority of patients, only a single intervention is required; however, a small minority can benefit from a revision tympanoplasty. In order to obtain these results, both the patient and the surgeon should engage in a long-term follow-up.