Faculty Bibliography

The mal de debarquement syndrome (MdDS), a continuous feeling of swaying, rocking, and/or bobbing, generally follows travel on the sea. The associated symptoms cause considerable distress. The underlying neural mechanisms are unknown, and to date there have been no effective treatments for this condition. Results in monkeys and humans suggested that MdDS was caused by maladaptation of the vestibulo-ocular reflex (VOR) to roll of the head during rotation. We studied 24 subjects with persistent MdDS (3 males, 21 females; 19.1 +/- 33 months). Physical findings included body oscillation at 0.2 Hz, oscillating vertical nystagmus when the head was rolled from side-to-side in darkness, and unilateral rotation during the Fukuda stepping test. We posited that the maladapted rocking and the physical symptoms could be diminished or extinguished by readapting the VOR. Subjects were treated by rolling the head from side-to-side while watching a rotating full-field visual stimulus. Seventeen of the 24 subjects had a complete or substantial recovery on average for approximately 1 year. Six were initially better, but the symptoms recurred. One subject did not respond to treatment. Thus, readaptation of the VOR has led to a cure or substantial improvement in 70% of the subjects with MdDS. We conclude that the adaptive processes associated with roll-while-rotating are responsible for producing MdDS, and that the symptoms can be reduced or resolved by readapting the VOR.

Objective. Sleep disturbances are common in patients with carpal tunnel syndrome (CTS). This study investigates the impact of CTS on sleep quality and clarifies the magnitude of this relationship. Methods. This is a prospective investigation of patients with CTS. Patients responded to the Levine-Katz Carpal Tunnel and the Pittsburgh Sleep Quality Index (PSQI) questionnaires to assess symptom severity and quality, respectively. Descriptive and bivariate analyses summarized the findings and assessed the correlations between CTS severity and sleep quality parameters. Results. 66 patients (53F, 13M) were enrolled. Patients reported a sleep latency of 30.0 (+/-22.5) minutes, with a total sleep time of 5.5 (+/-1.8) hours nightly. Global PSQI score was 9.0 (+/-3.8); 80% of patients demonstrated a significant reduction in sleep quality (global PSQI score >5). Increased CTS symptom and functional severity both resulted in a significant reduction in quality and time asleep. Both significantly correlated with subjective sleep latency, sleep disturbance, use of sleep promoting medications, daytime dysfunction, and overall global PSQI score. Conclusions. The findings confirm the correlation of sleep disturbances to CTS, that is, significant reduction of sleep duration and a correlation to sleep quality. Patients sleep 2.5 hours less than recommended and are at risk for comorbid conditions.

OBJECT/OBJECTIVE:Endoscopic endonasal treatment of petrous apex cholesterol granulomas allows for a natural drainage pathway into the nasopharynx. Because of the limited number of case series in the literature, there is limited evidence of recurrence rates and outcomes following endoscopic endonasal management. The purpose of this study was to determine the surgical outcomes of endoscopic endonasal approaches in the treatment of cholesterol granulomas of the petrous apex. METHODS:A systematic literature review was performed using PubMed for articles published from January 1980 to April 2014 to identify all studies reporting outcomes for endoscopic endonasal surgical management of cholesterol granulomas of the petrous apex. Operative approach, use of a stent, symptom outcome, restenosis, cyst recurrence, reoperation, and complications were extracted from included studies. RESULTS:A total of 53 patient cases were included from 22 relevant studies. The mean age was 41 years, and 26 patients (49%) were female. Stents were used in 45.1% of cases. Symptom resolution or improvement was seen in 98.6% of cases at follow-up (mean follow-up 20 months). Complications were reported in 13.2% of cases, with the most common complication being epistaxis. Restenosis on follow-up office endoscopic examination occurred in 9 of 45 cases (20.0%). Only 4 of these restenosis cases resulted in symptomatic cyst recurrence, resulting in an overall recurrence rate of 7.5%. The mean time from surgery to cyst recurrence was 13.5 months. The rate of symptomatic cyst recurrence was 10.7% in cases without the use of a stent compared with 4.3% in cases with stent placement (p = 0.6). CONCLUSIONS:Based on current literature, endoscopic endonasal approaches result in a high rate of symptom improvement or resolution. Complication rates are lower than prior case series that have utilized open approaches. Asymptomatic restenosis can be managed conservatively, since it is associated with symptomatic cyst recurrence less than half of the time. This study revealed a nonsignificant trend toward a decrease in symptomatic cyst recurrence when a stent was used, but further work is needed to clarify its impact.

The programming of CIs is essential for good performance. However, no Good Clinical Practice guidelines exist. This paper reports on the results of an inventory of the current practice worldwide. A questionnaire was distributed to 47 CI centers. They follow 47600 recipients in 17 countries and 5 continents. The results were discussed during a debate. Sixty-two percent of the results were verified through individual interviews during the following months. Most centers (72%) participated in a cross-sectional study logging 5 consecutive fitting sessions in 5 different recipients. Data indicate that general practice starts with a single switch-on session, followed by three monthly sessions, three quarterly sessions, and then annual sessions, all containing one hour of programming and testing. The main focus lies on setting maximum and, to a lesser extent, minimum current levels per electrode. These levels are often determined on a few electrodes and then extrapolated. They are mainly based on subjective loudness perception by the CI user and, to a lesser extent, on pure tone and speech audiometry. Objective measures play a small role as indication of the global MAP profile. Other MAP parameters are rarely modified. Measurable targets are only defined for pure tone audiometry. Huge variation exists between centers on all aspects of the fitting practice.

Sensory experience during early development can shape the central nervous system and this is thought to influence adult perceptual skills. In the auditory system, early induction of conductive hearing loss (CHL) leads to deficits in central auditory coding properties in adult animals, and this is accompanied by diminished perceptual thresholds. In contrast, a brief regimen of auditory training during development can enhance the perceptual skills of animals when tested in adulthood. Here, we asked whether a brief period of training during development could compensate for the perceptual deficits displayed by adult animals reared with CHL. Juvenile gerbils with CHL, and age-matched controls, were trained on a frequency modulation (FM) detection task for 4 or 10 days. The performance of each group was subsequently assessed in adulthood, and compared to adults with normal hearing (NH) or adults raised with CHL that did not receive juvenile training. We show that as juveniles, both CHL and NH animals display similar FM detection thresholds that are not immediately impacted by the perceptual training. However, as adults, detection thresholds and psychometric function slopes of these animals were significantly improved. Importantly, CHL adults with juvenile training displayed thresholds that approached NH adults. Additionally, we found that hearing impaired animals trained for 10 days displayed adult thresholds closer to untrained adults than those trained for 4 days. Thus, a relatively brief period of auditory training may compensate for the deleterious impact of hearing deprivation on auditory perception on the trained task.

Principal neurons of the lateral superior olivary nucleus (LSO) respond selectively to interaural level differences (ILD). To perform this computation, LSO neurons integrate excitatory synaptic drive from the ipsilateral ear with inhibitory synaptic drive from the contralateral ear via the medial nucleus of the trapezoid body (MNTB). Previous research demonstrated that inhibitory terminals from the MNTB to the LSO are eliminated during development. Furthermore, MNTB synapses display an activity- and age-dependent long-term depression (iLTD) that may contribute to inhibitory synapse elimination. However, inhibitory synapses that are stabilized become stronger. Here, we asked whether MNTB synapses displayed activity-dependent strengthening. Whole-cell recordings were obtained from LSO neurons in a gerbil brain slice before and after hearing onset. The inhibitory MNTB afferents were stimulated at a low rate, similar to spontaneous discharge rates observed in vivo. The MNTB-evoked inhibitory responses were strengthened by 40-300% when synaptic activity was coupled with postsynaptic membrane depolarization, exogenous glutamate application, or activation of ipsilateral excitatory synaptic inputs. This inhibitory long-term potentiation (iLTP) was associated with increased spontaneous inhibitory postsynaptic current (IPSC) amplitude and frequency. One hour after iLTP induction, IPSCs could not be de-potentiated by the MNTB stimulation pattern that induces iLTD in control slices. iLTP could only be induced after hearing onset (>P12), and was blocked in the presence of a GABAB receptor antagonist. Together, these results suggest a developmental period during which the induction of iLTP depends on the conjoint activation of GABAB receptors and postsynaptic depolarization. We propose that iLTP may support stabilization of un-pruned MNTB connections and contribute to the emergence of ILD processing in the mature LSO.

BACKGROUND: Oral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and tolerability of AG013, an oral rinse containing recombinant Lactococcus lactis secreting mucosal protectant human trefoil factor 1 (hTFF1), was evaluated in a phase 1b study in LAHNC subjects who received induction with cisplatin, 5-fluorouracil, with or without docetaxel. Preliminary efficacy data were also obtained. METHODS: A total of 25 of 52 LAHNC subjects who were followed during induction cycle 1 developed ulcerative oral mucositis (UOM; World Health Organization grade > 2) and were randomized to AG013:placebo (5:2 ratio) for cycle 2. Dosing schedules of 1, 3, or 6 times daily were evaluated (2 x 10(11) , 6 x 10(11) , and 1.2 x 10(12) colony forming units per day, respectively). OM was evaluated daily from cycle 2, day 1 through 14, using World Health Organization criteria. Pharmacokinetic assessment was also conducted. RESULTS: AG013 bacteria were not detected in blood. Oral live AG013 bacterial and hTFF1 levels in saliva and oral mucosa were equivalent among treatment groups. The most frequently occurring adverse events were nausea, oral pain, fatigue, diarrhea, and mucosal inflammation. Only 12% (3 of 25 adverse events), mainly nausea, were attributed to the investigational medicinal product: AG013 or placebo. Efficacy analysis showed a 35% reduction in percentage of days with UOM in AG013-subjects versus placebo. All placebo subjects experienced >/= 2 days of UOM, whereas 29% of AG013 subjects had UOM for 0 or 1 day. AG013 use resulted in fewer unscheduled office and emergency room visits. No differences were noted in mouth and throat soreness, opioid use, or gastrostomy tube placement. CONCLUSIONS: AG013 was safe and well tolerated. Preliminary efficacy data support further study.