Iatrogenic facial nerve injuries during chronic otitis media surgery: a multicentre retrospective study.

OBJECTIVES: To give an insight into why, when and where iatrogenic facial nerve (FN) injuries may occur and to explain how to deal with them in an emergency setting. DESIGN AND SETTING: Multicentre retrospective study in eight tertiary referral hospitals over 17 years. PARTICIPANTS: Twenty patients with partial or total FN injury during surgery for chronic otitis media (COM) were revised. MAIN OUTCOME MEASURES: Indication and type of surgery, experience of the surgeon, intra- and postoperative findings, value of CT scanning, patient management and final FN outcome were recorded. RESULTS: In 12 cases, the nerve was completely transected, but the surgeon was unaware in 11 cases. A minority of cases occurred in academic teaching hospitals. Tympanic segment, second genu and proximal mastoid segments were the sites involved during injury. The FN was not deliberately identified in 18 patients at the time of injury, and nerve monitoring was only applied in one patient. Before revision surgery, CT scanning correctly identified the lesion site in 11 of 12 cases and depicted additional lesions such as damage to the lateral semicircular canal. A greater auricular nerve graft was interposed in 10 cases of total transection and in one partially lesioned nerve: seven of them resulted in an HB III functional outcome. In two of the transected nerves, rerouting and direct end-to-end anastomosis was applied. A simple FN decompression was used in four cases of superficially traumatised nerves. CONCLUSIONS: We suggest checklists for preoperative, intraoperative and postoperative management to prevent and treat iatrogenic FN injury during COM surgery.

[Intraoperative parathyroid hormone measurement is the best predictor of postoperative symptomatic hypocalcemia]. / Die intraoperative Parathormonmessung als bester Indikator einer postoperativen symptomatischen Hypokalzämie.

BACKGROUND: The goal of this study is to evaluate risk factors for transient postoperative hypocalcemia (HC) and to define cutoff values for perioperative parathyroid hormone (PTH) and calcium parameters (Ca) to reduce the morbidity of symptomatic HC. MATERIALS AND METHODS: At our tertiary referral hospital (Luzerner Kantonsspital, Switzerland), a total of 353 patients underwent total thyroidectomy between 2006 and 2013 and were analyzed retrospectively in terms of HC risk. The serum values of calcium and PTH were measured at strictly defined time intervals, and patients' symptoms and the necessity of treatments were determined from patients' charts. RESULTS: The prevalence of transient postoperative HC was 43%; however, only 10% of patients were symptomatic. Significant risk factors for serum and symptomatic HC were calcium values (pre-, intra-, 4 h and 1 d postoperative), PTH values (intraoperative, 4 h and 1 d postoperative), and PTH decline. Interestingly, preoperative PTH values, patient age, weight of the thyroid gland, diagnosis, and sex were not significant risk factors. In the ROC analysis ('receiver operating characteristics'), calcium measurement 4 h postoperatively showed the best predictive ability for detecting serum HC, whereas intraoperative PTH measurements were predictive for symptomatic HC. CONCLUSION: Calcium and PTH values as well as PTH decline are significant risk factors for postoperative HC. Preoperatively, only calcium measurement is prognostically significant. Intraoperative PTH measurement is the most reasonable and sensitive factor for early recognition of temporary postoperative HC in the clinical setting.

Subtotal Petrosectomy and Cochlear Implant Placement in Otologic Presentation of "Wegener's Granulomatosis".

Granulomatosis with polyangitis is a rare granuloma forming necrotizing vasculitis, which involves mainly the respiratory tract and renal system. Otologic involvement may occur primarily as chronic serous otitis media and chronic silent mastoiditis with conductive hearing loss and may rarely lead to sensorineural hearing loss requiring cochlear implantation. This case describes a patient with granulomatous poylangitis with profound sensorineural hearing loss who underwent subtotal petrosectomy with cochlear implantation.

[Clinical Aspects of Cochlear Implantation in Meniere's Disease and After Labyrinthectomy]. / Klinische Aspekte der Cochleaimplantation bei Morbus Menière sowie nach Labyrinthektomie.

Objective: Due to the natural aging and the loosened CI-implantation criteria more formerly operated Meniere's patients will be supplied with a cochlear implant. However, it raises the question whether an implantation in a previously treated ear is promising. Material and Methods: Based on 2 cases in which we have carried out a CI-implantation, one of them 10 years after transmastoidal labyrinthectomy, and based on the current literature we draw attention to problems and prospects of success. Discussion: Histological studies show only a small ossification of the cochlea after labyrinthectomy. Implanted Meniere's patients have a better speech intelligibility than other CI users. Attacks of rotatory vertigo with tinnitus and fluctuations of hearing after cochlear implantation in Meniere's patients are rare or they are too little described. Conclusion: There is a trend to perform a simultaneous labyrinthectomy and cochlea implantation in Meniere's patients with desabling vertigo which have not responded to drug treatment. A formerly performed transmastoidal labyrinthectomy is not a contraindication for a cochlear implantation.

[Neuroendocrine adenoma of the middle ear]. / Neuroendokrine Adenome im Mittelohr.

BACKGROUND: Neuroendocrine adenomas of the middle ear are rare, low-grade neoplasms with potential for recurrence and metastasis. The nonspecific symptoms and preliminary clinical and radiological findings are misleading and often fail to provide the right diagnosis. PATIENTS AND METHODS: We analyzed the findings of 3 adult patients, who were treated between 2001 and June /2012 at the Luzerner Kantonsspital in Switzerland. RESULTS: The 3 patients reported on hearing loss, ear pressure and/or tinnitus. Otoscopy showed a thickened, intact tympanic membrane with a whitish-grayish prolapsing mass. All the patients had conductive hearing loss. Computer tomography showed an unspecified well-circumscribed soft-tissue mass. Definitive histology with immunostaining after radical tumor removal led to the proper diagnosis. CONCLUSIONS: The typical constellation of nonspecific clinical and radiological findings leads to the right diagnosis of neuroendocrine adenoma of the middle ear. After reviewing the literature, we illustrate the differential diagnosis as well as the relevant diagnostic and therapeutic procedures, and remind ENT physicians about this rare disease entity.

[Intratympanic steroid administration: use in the treatment of profound idiopathic sudden sensorineural hearing loss]. / Intratympanale Dexamethasongabe: Nutzen in der Behandlung des hochgradigen Hörsturzes.

BACKGROUND: Therapy for idiopathic sudden sensorineural hearing loss is still controversial. Although there are no evidenced-based studies, therapy with systemic steroids is widely accepted as the gold standard. Intratympanic administration of steroids appears to be an alternative or additional method of management without the disadvantage of systemic side effects and, therefore, makes therapy accessible for patients with contraindication for systemic steroids. MATERIAL AND METHODS: This retrospective analysis compares the audiometric results of 25 patients who were treated with standard therapy (prednisolone, hydroxyethyl starch, pentoxyfylline) with 23 patients who additionally received intratympanic steroids (IT group). A total of 4 injections were administered within 10 days. The solution used consisted of 0.3 ml dexamethasone (8 mg/ml) and 0.2 ml hyaluronic acid 0.2%. The pure-tone average (PTA) was evaluated prior to and 3 months after treatment. RESULTS: The PTA 3 months after treatment showed an improvement of 48 dB in the IT group and 38 dB in the standard treatment group. The IT group achieved better recovery with an average PTA improvement of 68% compared to the standard treatment group with an average improvement of 59%. Neither result reached significance. CONCLUSION: Combination therapy with intratympanic steroids showed a tendency for better hearing results without serious side effects. However, because current evidence is not adequate, randomized placebo-controlled multicenter studies are needed.

Impact of manual crimping on stapedotomy outcomes.

BACKGROUND: The impact of tight stapes crimping on hearing is a matter of debate. Several studies postulate that tight crimping is essential for lifelong success, whereas others have debated whether firm attachment leads to incus necrosis. Several types of prostheses with different coupling mechanisms have been developed, and manual crimping remains the most frequently used technique. This study investigates whether tightness really does affect hearing outcome. METHODS: The hearing results of patients who underwent primary stapedotomies using three different titanium pistons were analysed. The surgeons categorised the firmness of the piston attachment into 'tight' and 'loose' crimping groups. Hearing outcome and reasons for revision surgical procedures were investigated. RESULTS: The mean post-operative air-bone gap for frequencies of 0.5-4 kHz was 8.80 dB for the tight crimping group (n = 308) and 9.55 dB for the loose crimping group (n = 39). No significant difference was found (p = 0.4650). Findings at revision procedures were comparable (1.6 per cent vs 5 per cent). CONCLUSION: Although firm crimping is strongly advised, a movable loop upon palpation does not lead to unsatisfactory hearing results, and does not mandate piston replacement or bone cement use.

Congenital aural atresia: hearing rehabilitation using active middle-ear implants.

OBJECTIVE: To assess hearing rehabilitation in patients with congenital aural atresia using an active middle-ear implant (Vibrant Soundbridge). METHODS: Of a cohort of 70 microtia and atresia patients, 10 underwent Vibrant Soundbridge implantation between 2008 and 2021. Two of the 10 patients had binaural implantation, resulting in 12 ears for analysis. Pre- and post-operative audiometry data were analysed, and patient satisfaction was evaluated. Surgical issues regarding coupling sites and outcomes were analysed. RESULTS: Pure tone average (0.5, 1, 2 and 4 kHz) improved from a pre-operative mean (standard deviation) of 65.3 (8.7) dB HL to a post-operative mean of 26.8 (4.9) dB HL. This resulted in a mean pure tone average gain of 38.5 dB HL. The results indicate no obvious difference between stapes (n = 8) and incus (n = 4) coupling. The mean effective gain for 0.5, 1, 2 and 4 kHz was -17.8 dB HL (standard deviation = 4.3). Concerning effective gain, Vibrant Soundbridge performed best at 2 kHz. Patients reported high overall satisfaction, good sound quality and strongly improved directional hearing. CONCLUSION: An active middle-ear implant (Vibrant Soundbridge) allows hearing rehabilitation in selected atretic ears, and provides long-term hearing stability in children and adults.

[Temporal bone surgery. Surgical sequelae and complications]. / Felsenbeinchirurgie. Komplikationen und unerwünschte Operationsfolgen.

The saying "no surgery, no surgical complications" is certainly true for all specialties. Three categories of undesired events may occur following surgery: surgical sequelae, failure to cure and complications. A critical self-analysis of surgical complications often reveals that these arise in vexing fashion according to Murphy's law, i.e. "what can go wrong, will go wrong". Incomplete preoperative evaluation, insufficient exposure of the surgical field, failure to identify surgical landmarks and misjudgment of the patient's preoperative complaints may culminate in an undesired surgical outcome. Modern preoperative radiology, the possibilities of actual or even virtual temporal bone drilling in the laboratory and the surgeon's level of experience all ensure the relative rarity of relevant surgical complications in otology.

Correlation between tympanometry volume and three-dimensional computed tomography mastoid volumetry in tympanoplasty candidates.

OBJECTIVE: Ventilation of the middle ear and mastoid air cells is believed to play an important role in the pathogenesis of chronic ear disease. Traditionally, ventilation is assessed by computed tomography. However, this exposes patients to cumulative radiation injury. In cases with a perforation in the tympanic membrane, tympanometry potentially presents a non-invasive alternative to measure the ventilated middle-ear and mastoid air cell volume. This study hypothesised that total tympanometry volume correlates with ventilated middle-ear and mastoid air cell volume. METHOD: Total tympanometry volume was compared with ventilated middle-ear and mastoid air cell volume on computed tomography scans in 20 tympanic membrane perforations. RESULTS: There was a high correlation between tympanometry and computed tomography volumes (r = 0.78; p < 0.001). A tympanometry volume more than 2 ml predicted good ventilation on computed tomography. CONCLUSION: These results may help reduce the need for pre-operative computed tomography in uncomplicated cases with tympanic membrane perforations.

[Role of minimal invasive surgery for primary and secondary hyperparathyroidism]. / Stellenwert der minimal-invasiven Chirurgie beim primären und sekundären Hyperparathyroidismus.

BACKGROUND: The standard surgical approach to treat primary (pHPT) and secondary hyperparathyroidism (sHPT) used to be a cervicotomy with exploration of all four parathyroid glands. This access has been challenged recently by the introduction of minimally invasive techniques in order to achieve superior cosmesic results and to reduce theatre time. We analyzed the advantages and morbidities of these surgical aproaches. PATIENTS AND METHODS: Between 1997 and 2006 a total of 123 patients (109 with pHPT and 14 with sHPT) underwent parathyroidectomy at the ENT Department in Luzern. Ultrasonographic scanning was performed on 74 patients (68%), szintigraphy in 8 patients (7%) and both scanning methods in 27 patients (25%). 103 patients were available for follow-up. The indications for each technique were reviewed and outcome measures included serum Calcium and parathyroid hormone levels. RESULTS: Sensitivity for preoperative ultrasonographic and scintigraphic scanning was 67% and 65% for identification of the correct quadrant and 74% and 71% for identification of the correct side. A bilateral exploration was performed until June 2001 for all patients. Thereafter, a minimally invasive approach was chosen for patients with pHPT, whereas patients with sHPT still require bilateral exploration. Adequate preoperative localization was a prerequisite for a minimally invasive technique. Mean postoperative serum Kalzium levels were within the normal range, independently of the surgical technique and disease. Two patients developed hypercalcemia after an initially successful operation. CONCLUSIONS: Review of the literature confirms the shift from bilateral exploration towards minimally invasive techniques. The incidence of persistent or recurrent disease as well as the rate of complications seems comparable. Operation time for minimally invasive techniques is reduced in the hands of an experienced surgeon. However, proper preoperative localization of the diseased parathyroid gland is not always possible and the expenses of intraoperative parathyroid hormone measures do not lower the overall costs. Considerable experience and a multidisiplinary approach (endocrinologist, surgeon, pathologist) is required to adopt efficient minimally invasive techniques. As for sHPT, bilateral exploration remains the treatment of choice.

Herpes virus and Ménière's disease.

OBJECTIVE: The main goal of this study was to examine the vestibular ganglia from patients with intractable classic Ménière's disease (MD) for the presence or absence of DNA from three neurotropic viruses herpes simplex virus 1 and 2 (HSV1, HSV2) and varicella zoster virus (VZV) and to investigate the hypothesis that MD is associated with virus reactivation within Scarpa's ganglion. STUDY DESIGN: Polymerase chain reaction (PCR) was performed with nested primer sets specific for viral genomic DNA of HSV1, HSV2 and VZV in biopsies of the ganglion scarpae of patients with MD who underwent vestibular neurectomy. Included were patients with MD classified as definite MD according to American Academy of Otolaryngology/Head and Neck Surgery criteria. The ganglion scarpae and ganglion geniculi harvested at autopsy from patients without history of MD or facial palsy served as control specimens. RESULTS: No viral DNA was detected in the vestibular ganglion of 7 patients with definite MD. In 34% of the vestibular ganglia of the control group we detected either HSV1 or VZV. Only one Scarpa's ganglion had both viruses present at the same time. Thirty-two out of 34 ganglia from the geniculate segment of the facial nerve contained either HSV1 and/or VZV genomic DNA. Eight specimens contained both viruses simultaneously. Altogether viral DNA was found in 94% of ganglia. Viral genomic DNA of HSV2 was not detected. CONCLUSION: Although HSV and VZV appear to be present in many ganglion cells throughout the human body, we were unable to find genomic DNA of these viruses in patients with definite MD and disabling vertigo, who underwent vestibular neurectomy. Based on these results, reactivation of HSV1 and VZV in the vestibular ganglion does not seem to play a role in the pathogenesis of MD.

[Significance of computed tomography evaluation before revision stapes surgery]. / Stellenwert der CT-Diagnostik vor Revisions-Stapedotomien.

BACKGROUND: Stapedectomy and, more recently, stapedotomy have been widely accepted as the primary surgical techniques to improve conductive hearing in patients suffering from otosclerosis. Unsuccessful outcomes are infrequent, but revision surgery may become necessary. We have analyzed the value of computed tomography (CT) scanning following unsuccessful stapes surgery. PATIENTS AND METHODS: In a total of 37 CT scans, the depth of insertion, angle between prosthesis and footplate, location of prosthesis within the oval niche, visibility of the prosthesis, dehiscence of the superior semicircular canal, and extent of otospongiotic foci were evaluated and compared with the audiometric results. RESULTS: There was no significant correlation between CT parameters and audiologic results, except for patients with cochlear otosclerosis or lateral dislocation of the piston. One previously unknown dehiscence of the superior semicircular canal was diagnosed. Otospongiotic foci were seen in 13 ears (35%). CONCLUSION: Displacements of the stapes piston and rare causes for an insufficient result, such as a dehiscence of the superior semicircular canal, can be diagnosed accurately by CT. However, correlation between the audiologic results and the findings on CT scans was possible in only a few cases. Nevertheless, CT scans provide additional information for surgical planning in revision stapes surgery and may become increasingly important to reduce unanticipated intraoperative risks; they may even guide the surgeon not to perform unnecessary revision surgeries.

Effects of a sensory branch to the posterior external ear canal: coughing, pain, Ramsay Hunt's syndrome and Hitselberger's sign.

BACKGROUND: A distinct nerve innervating the external auditory canal can often be identified in close relation to the facial nerve when gradually thinning the posterior canal wall. This nerve has been attributed to coughing during cerumen removal, neuralgic pain, Hitselberger's sign and vesicular eruptions described in Ramsay Hunt's syndrome. This study aimed to demonstrate the origin and clinical impact of this nerve. METHODS AND RESULTS: In patients with intractable otalgia or severe coughing whilst inserting a hearing aid, who responded temporarily to local anaesthesia, the symptoms could be resolved by sectioning a sensory branch to the posterior canal. In a temporal bone specimen, it was revealed that this nerve is predominantly a continuation of Arnold's nerve, also receiving fibres from the glossopharyngeal nerve and facial nerve. Histologically, the communicating branch from the facial nerve was confirmed. CONCLUSION: Surgeons should be aware of the posterior auricular sensory branch and its clinical implications.

New potential binding determinant for hERG channel inhibitors.

Human ether-à-go-go related gene (hERG) 1 channels conduct the rapid delayed rectifier K(+) current (IKr) and are essential for the repolarization of the cardiac action potential. hERG1 inhibition by structurally diverse drugs may lead to life threatening arrhythmia. Putative binding determinants of hERG1 channel blockers include T623, S624 and V625 on the pore helix, and residues G648, Y652 and F656, located on segment S6. We and others have previously hypothesized that additional binding determinants may be located on helix S5, which is in close contact with the S6 segments. In order to test this hypothesis, we performed a detailed investigation combining ionic current measurements with two-microelectrode voltage clamp and molecular modeling techniques. We identified a novel aromatic high affinity binding determinant for blockers located in helix S5, F557, which is equally potent as Y652. Modeling supports a direct interaction with the outer pore helix.

Analysis of factors that correlate with mucositis in recipients of autologous and allogeneic stem-cell transplants.

PURPOSE: To identify predictors of oral mucositis and gastrointestinal toxicity after high-dose therapy. PATIENTS AND METHODS: Mucositis and gastrointestinal toxicity were prospectively evaluated in 202 recipients of high-dose therapy and autologous or allogeneic stem-cell rescue. Of 10 outcome variables, three were selected as end points: the peak value for the University of Nebraska Oral Assessment Score (MUCPEAK), the duration of parenteral nutritional support, and the peak daily output of diarrhea. Potential covariates included patient age, sex, diagnosis, treatment protocol, transplantation type, stem-cell source, and rate of neutrophil recovery. The three selected end points were also examined for correlation with blood infections and transplant-related mortality. RESULTS: A diagnosis of leukemia, use of total body irradiation, allogeneic transplantation, and delayed neutrophil recovery were associated with increased oral mucositis and longer parenteral nutritional support. No factors were associated with diarrhea. Also, moderate to severe oral mucositis (MUCPEAK > or = 18 on a scale of 8 to 24) was correlated with blood infections and transplant-related mortality: 60% of patients with MUCPEAK > or = 18 had positive blood cultures versus 30% of patients with MUCPEAK less than 18 (P =.001); 24% of patients with MUCPEAK > or = 8 died during the transplantation procedure versus 4% of patients with MUCPEAK less than 18 (P =.001). CONCLUSION: Gastrointestinal toxicity is a major cause of transplant-related morbidity and mortality, emphasizing the need for corrective strategies. The peak oral mucositis score and the duration of parenteral nutritional support are useful indices of gastrointestinal toxicity because these end points are correlated with clinically significant events, including blood infections and treatment-related mortality.

Calcium and facilitation at two classes of crustacean neuromuscular synapses.

The closer muscle of the crab, Chionoecetes, has at least two classes of excitatory neuromuscular synapses. In one class of synapses an action potential depolarizing the synaptic region releases much more transmitter if it has been preceded recently by another action potential. The other class of synapses shows this property, called facilitation, to a far lesser extent. Immediately after one conditioning stimulus the level of facilitation is similar in both classes. The rate of the ensuing decay of the facilitation is the critical factor differentiating the two classes of synapses. The relationship between external Ca(++) concentration and transmitter release is similar for both classes of synapses. The slope of a double logarithmic plot of this relationship varies from 3.1 between 5 and 10 mM Ca(++) to 0.9 between 30 and 40 mM Ca(++). Facilitation does not significantly change when tested in external Ca(++) concentrations ranging from 7 to 30 mM. The extracellularly recorded nerve terminal action potential does not increase in amplitude during facilitation. The results suggest that the mechanism of synaptic facilitation is similar for both classes of synapses and occurs after the stage in transmitter release involving Ca(++).

The time course of miniature endplate currents and its modification by receptor blockade and ethanol.

Miniature endplate currents (MEPCs) recorded from mouse diaphragms with a point voltage clamp, without inhibition of acetylcholinesterase (AChE) and in the absence of any drug, showed in their decay phase consistent deviations from an exponential time course, consisting of (a) "curvature," a progressive increase of decay rate during most of the decay phase, followed by (b) "late" tails. Both phenomena persisted when MEPCs (and channel lifetime) were prolonged by ethanol. Curvature was increased by muscle fiber depolarization and decreased by hyperpolarization. Receptor blockade by (+)-tubocurarine, alpha-bungarotoxin, hexamethonium, or myasthenic IgG accelerated the decay of the main part of MEPCs and eliminated curvature; the time constant of MEPCs became close to the channel time constant. We conclude that curvature arises from repeated action of ACh with cooperativity in ACh-receptor interaction; the voltage sensitivity of curvature follows from the voltage sensitivity of channel closing. Ethanol, in addition to its effect to prolong channel lifetime, enhances the tendency of ACh to act more than once to open channels before being lost to the system. Analysis of the rising phase of the MEPC, in terms of driving functions, also indicated that ethanol promotes channel opening by ACh; this action can account for a substantial increase of MEPC height by ethanol when MEPCs are made small by receptor blockade. Driving functions were also voltage sensitive, in a manner indicating acceleration of channel opening, but reduction of channel conductance, with hyperpolarization. Poisoning or inhibition of AChE prolonged MEPCs without altering the duration of ionic channels. Since ethanol caused further prolongation of MEPCs after poisoning of AChE, with little change in MEPC height, we conclude that the extension of mean channel lifetime by ethanol is accompanied by a similar extension of ACh binding to receptors. After poisoning of AChE, MEPCs became very variable in time course and the decay rate (tau-1) was correlated with MEPC height with a slope of log tau vs. log height of 0.77 for MEPCs of greater than 60% mean size. This slope is larger than expected from cooperativity in ACh-receptor interaction. Correlation of tau and height of MEPCs also exists when AChE is intact; the slope of log tau vs. log height was 0.12 with or without prolongation of MEPCs by ethanol.

Identification of the putative binding pocket of valerenic acid on GABAA receptors using docking studies and site-directed mutagenesis.

BACKGROUND AND PURPOSE: ß2/3-subunit-selective modulation of GABAA receptors by valerenic acid (VA) is determined by the presence of transmembrane residue ß2/3N265. Currently, it is not known whether ß2/3N265 is part of VA's binding pocket or is involved in the transduction pathway of VA's action. The aim of this study was to clarify the localization of VA's binding pocket on GABAA receptors. EXPERIMENTAL APPROACH: Docking and a structure-based three-dimensional pharmacophore were employed to identify candidate amino acid residues that are likely to interact with VA. Selected amino acid residues were mutated, and VA-induced modulation of the resulting GABAA receptors expressed in Xenopus oocytes was analysed. KEY RESULTS: A binding pocket for VA at the ß(+) /α(-) interface encompassing amino acid ß3N265 was predicted. Mutational analysis of suggested amino acid residues revealed a complete loss of VA's activity on ß3M286W channels as well as significantly decreased efficacy and potency of VA on ß3N265S and ß3F289S receptors. In addition, reduced efficacy of VA-induced IGABA enhancement was also observed for α1M235W, ß3R269A and ß3M286A constructs. CONCLUSIONS AND IMPLICATIONS: Our data suggest that amino acid residues ß3N265, ß3F289, ß3M286, ß3R269 in the ß3 subunit, at or near the etomidate/propofol binding site(s), form part of a VA binding pocket. The identification of the binding pocket for VA is essential for elucidating its pharmacological effects and might also help to develop new selective GABAA receptor ligands.