Is Gulf War Illness a prolonged early phase tauopathy?

The work of the Gulf War Illness (GWI) Consortium and that of basic and clinical researchers across the USA have resulted in a better understanding in recent years of the pathological basis of GWI, as well as of the mechanisms underlying the disorder. Among the most concerning symptoms suffered by veterans with GWI are cognitive decrements including those related to memory functioning. These decrements are not severe enough to meet dementia criteria, but there is significant concern that the mild cognitive impairment of these veterans will progress to dementia as they become older. Recent studies on GWI using human brain organoids as well as a rat model suggest that one potential cause of the cognitive problems may be elevated levels of tau in the brain, and this is supported by high levels of tau autoantibodies in the blood of veterans with GWI. There is urgency in finding treatments and preventive strategies for these veterans before they progress to dementia, with added value in doing so because their current status may represent an early phase of tauopathy common to many neurodegenerative diseases.

Veteran-derived cerebral organoids display multifaceted pathological defects in studies on Gulf War Illness.

Approximately 30% of the veterans who fought in the 1991 Gulf War (GW) suffer from a disease called Gulf War Illness (GWI), which encompasses a constellation of symptoms including cognitive deficits. A coalescence of evidence indicates that GWI was caused by low-level exposure to organophosphate pesticides and nerve agents in combination with physical stressors of the battlefield. Until recently, progress on mechanisms and therapy had been limited to rodent-based models. Using peripheral blood mononuclear cells from veterans with or without GWI, we recently developed a bank of human induced pluripotent stem cells that can be differentiated into a variety of cellular fates. With these cells, we have now generated cerebral organoids, which are three-dimensional multicellular structures that resemble the human brain. We established organoid cultures from two GW veterans, one with GWI and one without. Immunohistochemical analyses indicate that these organoids, when treated with a GW toxicant regimen consisting of the organophosphate diisopropyl fluorophosphate (a sarin analog) and cortisol (to mimic battlefield stress), display multiple indicators consistent with cognitive deficits, including increased astrocytic reactivity, enhanced phosphorylation of tau proteins, decreased microtubule stability, and impaired neurogenesis. Interestingly, some of these phenotypes were more pronounced in the organoids derived from the veteran with GWI, potentially reflecting a stronger response to the toxicants in some individuals compared to others. These results suggest that veteran-derived human cerebral organoids not only can be used as an innovative human model to uncover the cellular responses to GW toxicants but can also serve as a platform for developing personalized medicine approaches for the veterans.

Development of a physiological model of human middle ear epithelium.

INTRODUCTION: Otitis media is an umbrella term for middle ear inflammation; ranging from acute infection to chronic mucosal disease. It is a leading cause of antimicrobial therapy prescriptions and surgery in children. Despite this, treatments have changed little in over 50 years. Research has been limited by the lack of physiological models of middle ear epithelium. METHODS: We develop a novel human middle ear epithelial culture using an air-liquid interface (ALI) system; akin to the healthy ventilated middle ear in vivo. We validate this using immunohistochemistry, immunofluorescence, scanning and transmission electron microscopy, and membrane conductance studies. We also utilize this model to perform a pilot challenge of middle ear epithelial cells with SARS-CoV-2. RESULTS: We demonstrate that human middle ear epithelial cells cultured at an ALI undergo mucociliary differentiation to produce diverse epithelial subtypes including basal (p63+), goblet (MUC5AC+, MUC5B+), and ciliated (FOXJ1+) cells. Mature ciliagenesis is visualized and tight junction formation is shown with electron microscopy, and confirmed by membrane conductance. Together, these demonstrate this model reflects the complex epithelial cell types which exist in vivo. Following SARS-CoV-2 challenge, human middle ear epithelium shows positive viral uptake, as measured by polymerase chain reaction and immunohistochemistry. CONCLUSION: We describe a novel physiological system to study the human middle ear. This can be utilized for translational research into middle ear diseases. We also demonstrate, for the first time under controlled conditions, that human middle ear epithelium is susceptible to SARS-CoV-2 infection, which has important clinical implications for safe otological surgery. LEVEL OF EVIDENCE: NA.

A cellular approach to understanding and treating Gulf War Illness.

Gulf War Illness (GWI), a disorder suffered by approximately 200,000 veterans of the first Gulf War, was caused by exposure to low-level organophosphate pesticides and nerve agents in combination with battlefield stress. To elucidate the mechanistic basis of the brain-related symptoms of GWI, human-induced pluripotent stem cells (hiPSCs) derived from veterans with or without GWI were differentiated into forebrain glutamatergic neurons and then exposed to a Gulf War (GW) relevant toxicant regimen consisting of a sarin analog and cortisol, a human stress hormone. Elevated levels of total and phosphorylated tau, reduced microtubule acetylation, altered mitochondrial dynamics/transport, and decreased neuronal activity were observed in neurons exposed to the toxicant regimen. Some of the data are consistent with the possibility that some veterans may have been predisposed to acquire GWI. Wistar rats exposed to a similar toxicant regimen showed a mild learning and memory deficit, as well as cell loss and tau pathology selectively in the CA3 region of the hippocampus. These cellular responses offer a mechanistic explanation for the memory loss suffered by veterans with GWI and provide a cell-based model for screening drugs and developing personalized therapies for these veterans.

Hereditary spastic paraplegia: gain-of-function mechanisms revealed by new transgenic mouse.

Mutations of the SPAST gene, which encodes the microtubule-severing protein spastin, are the most common cause of hereditary spastic paraplegia (HSP). Haploinsufficiency is the prevalent opinion as to the mechanism of the disease, but gain-of-function toxicity of the mutant proteins is another possibility. Here, we report a new transgenic mouse (termed SPASTC448Y mouse) that is not haploinsufficient but expresses human spastin bearing the HSP pathogenic C448Y mutation. Expression of the mutant spastin was documented from fetus to adult, but gait defects reminiscent of HSP (not observed in spastin knockout mice) were adult onset, as is typical of human patients. Results of histological and tracer studies on the mouse are consistent with progressive dying back of corticospinal axons, which is characteristic of the disease. The C448Y-mutated spastin alters microtubule stability in a manner that is opposite to the expectations of haploinsufficiency. Neurons cultured from the mouse display deficits in organelle transport typical of axonal degenerative diseases, and these deficits were worsened by depletion of endogenous mouse spastin. These results on the SPASTC448Y mouse are consistent with a gain-of-function mechanism underlying HSP, with spastin haploinsufficiency exacerbating the toxicity of the mutant spastin proteins. These findings reveal the need for a different therapeutic approach than indicated by haploinsufficiency alone.

The psychological health and well-being of emergency medicine consultants in the UK.

OBJECTIVE: To explore the experience of psychological distress and well-being in emergency medicine (EM) consultants. METHODS: A qualitative, interpretative phenomenological analysis (IPA) study based on 1:1 semistructured interviews with EM consultants working full time in EDs across South West England. Eighteen EM consultants were interviewed across five EDs, the mean (SD) age of participants being 43.17 (5.8) years. The personal meanings that participants attached to their experiences were inductively analysed. RESULTS: The analysis formed three superordinate themes: systemic pressures, physical and mental strain and managing the challenges. Pressures within the ED and healthcare system contributed to participants feeling undervalued and unsatisfied when working in an increasingly uncontrollable environment. Participants described working intensely to meet systemic demands, which inadvertently contributed to a diminishing sense of achievement and self-worth. Consultants perceived their experience of physical and emotional strain as unsustainable, as it negatively impacted; functioning at work, relationships, personal well-being and the EM profession. Participants described how sustainability as an EM consultant could be promoted by social support from consultant colleagues and the ED team, and the opportunity to develop new roles and support ED problem solving at an organisational level. These processes supported a stigma-reducing means of promoting psychological well-being. CONCLUSIONS: EM consultants experience considerable physical and mental strain. This strain is dynamically related to consultants' experiences of diminishing self-worth and satisfaction, alongside current sociopolitical demands on EM services. Recognising the psychological experiences and needs of EM consultants and promoting a sustainable EM consultant role could benefit individual psychological well-being and the delivery of emergency care.

Use of biosynthetic grafts (Omniflow II) for high infection risk haemodialysis vascular access.

PURPOSE: Infective complications of patients requiring insertion of arteriovenous grafts for hemodialysis remain a challenge. In particular, patients who have exhausted autologous options and have had recent infective complications relating to alternative dialysis modalities such as peritonitis or central venous catheter-associated bacteremia can pose a significant dilemma. We present a series of challenging cases that represent examples of the use of biosynthetic grafts in patients with on-going infective risks. A review of available literature for the use of the Omniflow II graft in dialysis access is included. METHODS: Electronic databases were searched for studies assessing the use of the Omniflow II graft for dialysis in accordance with PRISMA published up to 31st March 2014. The primary outcomes for this study were 1-year primary and secondary patency rates. Secondary outcomes were rates of infection and aneurysmal degeneration. RESULTS: Three cases are described that were considered at high risk of infection and all successfully managed with the Omniflow II arteriovenous graft (AVG). None showed signs of infection and all grafts were patent at three months' follow-up. On review of the literature and following strict criteria, four studies were included with a total of 236 procedures. We found that the one-year primary patency rate for Omniflow II AVGs was 60.1% (53.6-66.5) with a secondary patency rate of 82.1% (76.7-86.9). Infection rates are reported at 0% to 5.7%, with aneurysmal rates ranging between 0% and 6.8%. CONCLUSIONS: This small series reports on the successful use of the Omniflow II graft in patients with high risk of infection and, whilst limited in its size and scientific design, it does support the limited existing literature for the potential benefits of the biosynthetic approach where concerns regarding infective complications of synthetic material exist.

Investigation of variant Creutzfeldt-Jakob disease implicated organ or tissue transplantation in the United Kingdom.

BACKGROUND: Person-to-person transmission of variant Creutzfeldt-Jakob disease (vCJD) has occurred through blood transfusion and could also theoretically occur as a result of the transplantation of organs or tissues. This study aimed to investigate whether there were transplant-associated vCJD cases in the United Kingdom (UK). METHODS: Medical histories were reviewed for 177 UK vCJD cases to identify situations where the transplantation of organs or tissues might have occurred. A "look-back" was then performed to trace the respective donors or recipients of the implicated organ or tissue. RESULTS: A single patient had undergone an organ (liver) transplant before vCJD onset, from a donor who had died of causes unrelated to vCJD. The look-back was able to trace six other organ or tissue donations made by the same donor. No other situations were identified where the receipt or donation of organs or tissues had occurred in people who went on to develop vCJD. There was considered no need, on this particular occasion, to implement public health measures associated with the organ transplantation, beyond those already in place. CONCLUSIONS: This study provides no evidence of transplant-associated vCJD in the UK. It is, however, important to continue to seek to identify individuals who might be at risk of vCJD by this route so that appropriate public health measures can be implemented.

A behavioural dynamic model of the relative age effect.

The relationship between date of birth and success in a variety of sports, including hockey, is well established. This phenomenon is known as the relative age effect (RAE). We model the RAE in Canadian youth hockey as a positive feedback loop where an initial age advantage is reinforced through additional training and playing opportunities based on perceived skill superiority. The same causal mechanism leads to a higher quit rate for relatively younger players. Our model effectively replicates the birth month distribution of Canadian National Hockey League players (R2 = 86.79%) when driven by Canadian birth distributions. We use this model to evaluate three policies that aim to lessen the RAE. All of the policies reduce the RAE with a significant delay. The most effective policy is a combination of providing additional support to age disadvantaged children and rotating the cut-off date for youth leagues between January 1st and July 1st annually. In equilibrium, this approach leads to a 96% reduction in the RAE compared to the base case.

Otic langerhans' cell histiocytosis in an adult: a case report and review of the literature.

Objective. To present a case of otic Langerhans' cell histiocytosis in an adult. Also included the diagnosis and management of the condition and a review of the relevant literature. Case Report. We report a case of a 41-year-old man with a history of persistent unilateral ear discharge associated with an aural polyp. Radiological imaging showed bony lesions of the skull and a soft-tissue mass within the middle ear. Histological analysis of the polyp demonstrated Langerhans' cell histiocytosis. His otological symptoms were completely resolved with the systemic therapy. Conclusions. Otic Langerhans' cell histiocytosis can present in adults. Persistent ear symptoms along with evidence of soft-tissue masses within the ear and bony lesions of the skull or elsewhere should prompt the otolaryngologists to include Langerhans' cell histiocytosis in their differential diagnosis. Management should be with systemic therapy rather than local surgical treatment.

An investigation of factors supporting the psychological health of staff in a UK emergency department.

STUDY OBJECTIVE: Research indicates emergency department doctors experience high levels of stress. Poor psychological health affects staff well-being and patient care, with considerable organisational and financial cost. This study compares levels of psychological health in medical, nursing and administrative staff from a UK emergency department with an orthopaedic comparison department. The study investigates the influence of coping strategies and the support people receive from their colleagues (ie, social support). METHODS: Comparative design, using self-report questionnaires comparing emergency (n=73) and orthopaedic (n=63) staff. Measures included: General Health Questionnaire-12, Hospital Anxiety and Depression Scale, Brief COPE, and questions relating to social identity and social support. RESULTS: The proportion of staff experiencing clinically significant levels of distress was higher than would be expected in the general population. The increased risk of psychological distress previously shown for emergency doctors is not present here for other emergency staff members. Better psychological health was associated with greater use of problem-focused coping and less use of maladaptive coping. Social support was associated with better psychological health and greater use of problem-focused coping. CONCLUSIONS: Priority should be given to developing and evaluating interventions to improve psychological health for this group. Findings suggest that coping strategies and social support are important factors to incorporate into such interventions.

Infections and foreign bodies in ENT.

Infections play a major role in the practice of ENT. Microbial penetration into tissues of the head and neck can initiate a focal reaction causing superficial self-resolving infections. However, some of these have the potential to develop into life-threatening disease. We provide an overview of the most common ENT infections with focus on the presentation, diagnosis and management. Foreign bodies of the ear, nose and throat are a common presentation to primary and emergency care. Most commonly these are seen in children and include plastic toys, beads and foodstuffs inserted into the ears and nose. Diagnosis is often delayed as insertion is usually not witnessed. In exceptional cases airway foreign bodies can present as a life-threatening emergency. Removal of foreign bodies can usually be achieved by a skilled practitioner with minimal complications. Methods of removal include suction catheters, syringing, and use of instrumentation. In adults, the treatment of oesophageal food bolus obstruction may require a combination of medical and surgical intervention.

Errorless learning and spaced retrieval: how do these methods fare in healthy and clinical populations?

While errorless learning and spaced retrieval have both proved effective in helping many patients with acquired brain injury (ABI) and dementia learn novel information, it is not clear which of these principles we should apply to target treatment most effectively. To address this issue we conducted a systematic comparison of these principles in three experiments, comparing their effectiveness in healthy controls (N = 60), patients with ABI (N = 30), and patients with dementia (N = 15). Participants were asked to learn face-name associations, and the relative effectiveness of the principles over and above trial-and-error learning was investigated. The results were remarkably consistent across experiments: Both errorless learning and spaced retrieval produced greater accuracy in name recall than did trial-and-error learning, but recall under conditions of spaced retrieval was significantly better than that under errorless learning. We discuss the implications of these findings and suggest that spaced retrieval may be the stronger memory rehabilitation principle when it comes to learning face-name associations in people with mild to moderate memory impairment.

Efficacy and safety of inhaled zanamivir in the prevention of influenza in community-dwelling, high-risk adult and adolescent subjects: a 28-day, multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Influenza can cause significant morbidity and mortality in subjects at high risk for complications, including the elderly (age >or=65 years) and those with chronic respiratory, cardiovascular, or metabolic conditions. Effective prophylaxis can significantly reduce the disease burden in this population. Previous studies conducted primarily in non-high-risk subjects have reported the efficacy of inhaled zanamivir in preventing influenza. OBJECTIVE: This study investigated the efficacy and safety of zanamivir in preventing influenza in community-dwelling adult and adolescent subjects at high risk for complications of influenza. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study in community-dwelling subjects aged >or=12 years who were at high risk for developing complications of influenza, were able to use the Diskhaler device (Glaxo Group Limited, Research Triangle Park, North Carolina), and were able to take the first dose of study medication within 5 days of laboratory-confirmed local influenza activity. Eligible subjects were randomized to receive inhaled zanamivir 10 mg or placebo once daily for 28 days. The primary end point was the proportion of randomized subjects who developed symptomatic influenza during prophylaxis, as confirmed by culture and/or serology. All adverse events (AEs) occurring after the first dose of study medication were recorded. RESULTS: The study enrolled 3363 subjects, of whom 58% were female and 93% were white; the mean age of participants was 60.4 years (range, 12-94 years), and 4% were adolescents. Significantly fewer zanamivir-treated subjects developed symptomatic, laboratory- confirmed influenza during prophylaxis compared with placebo recipients (4/1678 vs 23/1685, respectively), representing a relative risk (RR) of 0.17 (95% CI, 0.07-0.44; P < 0.001) and a protective efficacy of 83%. The incidence of complications was reduced in zanamivir-treated subjects compared with placebo recipients (1/1678 and 8/1685), representing an RR of 0.12 (95% CI, 0.02-0.73; P = 0.042) and a protective efficacy of 88%. The numbers of zanamivir recipients (151/1678 [9%]) and placebo recipients (169/1685 [ 10 % ] ) who developed symptomatic influenza-like illness regardless of laboratory confirmation did not differ significantly (RR = 0.86; 95% CI, 0.70-1.06), indicating that zanamivir was not effective in preventing influenza-like illness that was not caused by influenza infection. Similarly, there was no significant difference in the numbers of zanamivir and placebo recipients who developed laboratory-confirmed infection regardless of symptoms (39/1678 [2%] and 52/1685 [3%], respectively; RR = 0.76; 95% CI, 0.50-1.15). Of these, 64 subjects (35 and 29) were asymptomatic; seroconversion occurred in all but 1 subject, indicating that zanamivir prophylaxis did not prevent asymptomatic seroconversion. During prophylaxis, 51% of subjects in both treatment groups reported at least 1 AE. There were no major differences in the frequency or nature of AEs between groups. The most commonly reported AEs (>or=3% of subjects in each treatment group) were consistent with upper respiratory viral infection (headache: 17% zanamivir, 18% placebo; cough: 14% and 15%, respectively; throat and tonsil discomfort/pain: 13% and 14%). There were no differences between groups in the overall incidence of viral respiratory infections (5% in both groups) or ear, nose, and throat infections (2% in both groups). None of the analyzed isolates from confirmed cases of influenza exhibited reduced susceptibility to zanamivir or genotypic evidence of resistance. CONCLUSIONS: Zanamivir, administered once daily for 28 days, was efficacious in preventing infection with the predominant circulating strains in the 2000- 2001 influenza season in the Northern Hemisphere (influenza A/New Calendonia/20/99-1ike and influenza B/ Sichuan/379/99-like) in these high-risk community- dwelling subjects aged >or=12 years. Zanamivir was well tolerated, with a safety profile comparable to that of placebo. No emergence of resistant virus was detected.

Is laryngopharyngeal reflux related to functional dysphonia?

OBJECTIVES: Laryngopharyngeal reflux (LPR) may be a contributing factor in chronic hoarseness. The association of LPR with functional dysphonia (FD), the most common voice clinic diagnosis, is unknown. We attempted to determine whether patients with FD have a higher rate of laryngeal exposure to acidic stomach contents than do healthy volunteers. METHODS: We recruited through the voice clinic 23 patients who had had persistent dysphonia for 3 months. Pregnancy, major structural laryngeal abnormality, and vocal fold paralysis were exclusion criteria. Eight healthy volunteers were recruited. The subjects gave informed consent to enter the study, which had the approval of our hospital ethics committee. The patients and control subjects underwent 24-hour dual-probe pH-metry. RESULTS: Twenty-two patients and 6 control subjects completed the study. Overall, there seemed to be no statistical differences between patients and controls on all but 2 channel 1 pH-metry parameters. These were the longest reflux episode (seconds) in a supine position, and the fraction of time the pH was less than 4 in a supine position. Both of these time periods were longer in patients than in the controls (p < .05). CONCLUSIONS: Our study demonstrated an association between LPR and FD for 2 pH parameters. Larger studies are required to assess the potential relationship between nonorganic dysphonias and reflux. Furthermore, the presence of a multifactorial causation of FD, including "medical" and psychological causes, should be addressed in future studies.

Spousal relationship satisfaction following acquired brain injury: the role of insight and socio-emotional skill.

Spousal relationships following brain injury are particularly vulnerable to strain and breakdown. Changes in personality and socio-emotional processing and behaviour have been implicated as causal factors. We examined spousal relationship satisfaction following an acquired brain injury to one partner. Couples affected by chronic pain and a group of healthy couples were used for comparison and control. Compared to healthy controls current satisfaction was poorer in the brain injury couples, and satisfaction with the relationship had reduced from pre to post-injury. We found an especially important role for empathy, which differentiated between the groups in terms of functioning and insight.

Modulation of conventional outflow facility by the adenosine A1 agonist N6-cyclohexyladenosine.

PURPOSE: Studies have shown that the activation of adenosine A(1) receptors lower intraocular pressure primarily by increasing total outflow facility. The purpose of this study was to investigate the actions of the adenosine A(1) agonist N(6)-cyclohexyladenosine (CHA) on conventional outflow facility. METHODS: Conventional outflow facility was evaluated in isolated bovine anterior segments, perfused at a constant pressure of 10 mm Hg. After overnight perfusion to establish a stable baseline, the concentration- and time-dependent changes in outflow facility induced by CHA were determined. To confirm the involvement of adenosine A(1) receptors and matrix metalloproteinases (MMP) in any change in facility, the responses to CHA were evaluated in preparations treated with the adenosine A(1) receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT), or the nonselective MMP inhibitor GM-6001. RESULTS: The administration of CHA (10 microM) to perfused anterior segments produced a 28% increase in outflow facility over basal levels. This response was relatively slow to develop with no significant change in outflow facility measured until after 60 minutes of CHA infusion. The peak response to CHA infusion occurred between 3 and 4 hours after CHA administration. Analysis of the CHA concentration-response curves demonstrated that this increase in outflow facility was concentration-dependent, with an EC(50) of 0.28 microM. Pretreatment with the adenosine A(1) receptor antagonist CPT (10 microM) or the nonselective MMP inhibitor GM-6001 (10 microM) blocked the response to CHA (1 microM). When compared with control eyes, no significant change in baseline facility was measured in eyes perfused with CPT or GM-6001. CONCLUSIONS: These studies demonstrate that the adenosine agonist CHA significantly increases conventional outflow facility in the perfused bovine eye. Analysis of the CHA concentration-response curve and inhibition of the CHA-induced increase in outflow facility by the adenosine A(1) antagonist confirms that this response is mediated by the activation of adenosine A(1) receptors. The inhibition of the CHA-induced increase in outflow facility by the MMP inhibitor GM-6001 provides evidence that the secretion and activation of MMPs within the conventional outflow pathway play a central role in the ocular hypotensive action of adenosine A(1) agonists.

Evidence supporting the inclusion of strains from each of the two co-circulating lineages of H3N8 equine influenza virus in vaccines.

Two lineages of antigenically distinct equine influenza A H3N8 subtype viruses, American and European, co-circulate. Experiments were conducted in ponies to investigate the protection induced by vaccines containing virus from one lineage against challenge infection with homologous or heterologous virus. Regression analysis showed that vaccinated ponies with average pre-challenge single radial haemolysis (SRH) antibody levels (i.e. 45-190mm2) had a higher probability of becoming infected if they were vaccinated with virus heterologous to the challenge strain than if they were vaccinated with homologous virus. Field studies in Thoroughbred racehorses also showed that SRH antibody levels of >/= 150mm2 induced by vaccines containing a European lineage strain are protective against infection with a virus from the same lineage, but that the same or higher antibody levels may not be protective against an American lineage virus. In conclusion, vaccines should contain virus strains representative of both H3N8 subtype lineages to maximise protection against infection.

Is it worthwhile to attempt hearing preservation in larger acoustic neuromas?

OBJECTIVE: To determine the hearing outcome in patients undergoing surgery via the retrosigmoid approach for acoustic neuromas with a substantial component in the cerebellopontine angle. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: The medical records of all patients undergoing acoustic neuroma removal via the retrosigmoid approach at a tertiary referral center were retrospectively reviewed. Sixty-four patients with both cerebellopontine angle component >or=15 mm and preoperative audiometry of class A or B (American Academy of Otolaryngology-Head and Neck Surgery) were identified. MAIN OUTCOME MEASURES: Postoperative average pure tone threshold and word recognition scores, categorized according to the classification of the American Academy of Otolaryngology-Head and Neck Surgery, were used to assess hearing outcome. RESULTS: Overall, only 6.3% (4 of 63) retained good hearing (class A or B) postoperatively. Hearing preservation rate in the smallest (15- to 19-mm) group was 17.6% (3 of 17), which was better than that for the larger groups. No successful hearing preservation was achieved in tumors with >or=25 mm cerebellopontine angle component (0 of 23). CONCLUSIONS: Surgeon and patient alike would always choose a hearing preservation technique if there was no potential for increased morbidity in making the attempt. When compared with the non-hearing preservation translabyrinthine approach, the retrosigmoid approach had a higher incidence of persistent headache. In addition, efforts to conserve the auditory nerve prolong operating time, increase the incidence of postoperative vestibular dysfunction, and carry a slightly higher risk of tumor recurrence. Nevertheless, even though the probability of success is disappointingly small, when excellent hearing is present we favor offering the option of a hearing conservation attempt when the patient has been well informed of the pros and cons of the endeavor. Factors weighing against undertaking this effort include larger cerebellopontine angle component (>or=25 mm), deep involvement of the fundus, wide erosion of the porus, and marginal residual hearing.