Effects of a mind-body program on symptoms of depression and perceived stress among adults with neurofibromatosis type 2 who are deaf: A live-video randomized controlled trial.

INTRODUCTION: Neurofibromatosis type 2 (NF2) is a rare, progressive and incurable genetic disorder associated with progressive hearing loss and eventual deafness. As a group, patients with NF report high levels of stress and depressive symptoms. However, no studies have explored improvement in these symptoms after psychosocial interventions. We have previously shown that a mind-body program tailored to adults with NF2 who are deaf (the Relaxation Response and Resiliency Program for Deaf NF2, d3RP-NF2) improves quality of life and resiliency over and above a Health Enhancement program when both are delivered via live-video and assisted by Communication Access Realtime Translation (CART). Here we tested the effects of the programs on depression and perceived stress. METHODS: Forty-five patients with NF2 and significant hearing loss were randomized to the d3RP-NF2 or Health-Enhancement program and completed measures of depression (PHQ-9) and perceived stress (PSS-10) at baseline, post-intervention, and six-month follow-up. RESULTS: Patients randomized to the d3RP-NF2 program, but not to the control condition, experienced significant decreases on both measures from baseline to post-test, which were maintained at follow-up (within group tests). However, improvements following the d3RP-NF2 program was not significantly higher than those observed in the control group (between group tests). CONCLUSION: Results provide the first evidence of improvement in symptoms of depression and perceived stress among deaf patients living with NF2 who participate in a virtual mind-body program.

Suggested deafness during hypnosis and simulation of hypnosis compared to a distraction and control condition: A study on subjective experience and cortical brain responses.

Hypnosis is a powerful tool to affect the processing and perception of stimuli. Here, we investigated the effects of hypnosis on the processing of auditory stimuli, the time course of event-related-potentials (ERP; N1 and P3b amplitudes) and the activity of cortical sources of the P3b component. Forty-eight participants completed an auditory oddball paradigm composed of standard, distractor, and target stimuli during a hypnosis (HYP), a simulation of hypnosis (SIM), a distraction (DIS), and a control (CON) condition. During HYP, participants were suggested that an earplug would obstruct the perception of tones and during SIM they should pretend being hypnotized and obstructed to hear the tones. During DIS, participants' attention was withdrawn from the tones by focusing participants' attention onto a film. In each condition, subjects were asked to press a key whenever a target stimulus was presented. Behavioral data show that target hit rates and response time became significantly reduced during HYP and SIM and loudness ratings of tones were only reduced during HYP. Distraction from stimuli by the film was less effective in reducing target hit rate and tone loudness. Although, the N1 amplitude was not affected by the experimental conditions, the P3b amplitude was significantly reduced in HYP and SIM compared to CON and DIS. In addition, source localization results indicate that only a small number of neural sources organize the differences of tone processing between the control condition and the distraction, hypnosis, and simulation of hypnosis conditions. These sources belong to brain areas that control the focus of attention, the discrimination of auditory stimuli, and the organization of behavioral responses to targets. Our data confirm that deafness suggestions significantly change auditory processing and perception but complete deafness is hard to achieve during HYP. Therefore, the term 'deafness' may be misleading and should better be replaced by 'hypoacusis'.

Auditory Neural Activity in Congenitally Deaf Mice Induced by Infrared Neural Stimulation.

To determine whether responses during infrared neural stimulation (INS) result from the direct interaction with spiral ganglion neurons (SGNs), we tested three genetically modified deaf mouse models: Atoh1-cre; Atoh1 f/f (Atoh1 conditional knockout, CKO), Atoh1-cre; Atoh1 f/kiNeurog1 (Neurog1 knockin, KI), and the Vglut3 knockout (Vglut3 -/-) mice. All animals were exposed to tone bursts and clicks up to 107 dB (re 20 µPa) and to INS, delivered with a 200 µm optical fiber. The wavelength (λ) was 1860 nm, the radiant energy (Q) 0-800 µJ/pulse, and the pulse width (PW) 100-500 µs. No auditory responses to acoustic stimuli could be evoked in any of these animals. INS could not evoke auditory brainstem responses in Atoh1 CKO mice but could in Neurog1 KI and Vglut3 -/- mice. X-ray micro-computed tomography of the cochleae showed that responses correlated with the presence of SGNs and hair cells. Results in Neurog1 KI mice do not support a mechanical stimulation through the vibration of the basilar membrane, but cannot rule out the direct activation of the inner hair cells. Results in Vglut3 -/- mice, which have no synaptic transmission between inner hair cells and SGNs, suggested that hair cells are not required.

Remodeling of Dendritic Spines in the Avian Vocal Motor Cortex Following Deafening Depends on the Basal Ganglia Circuit.

Deafening elicits a deterioration of learned vocalization, in both humans and songbirds. In songbirds, learned vocal plasticity has been shown to depend on the basal ganglia-cortical circuit, but the underlying cellular basis remains to be clarified. Using confocal imaging and electron microscopy, we examined the effect of deafening on dendritic spines in avian vocal motor cortex, the robust nucleus of the arcopallium (RA), and investigated the role of the basal ganglia circuit in motor cortex plasticity. We found rapid structural changes to RA dendritic spines in response to hearing loss, accompanied by learned song degradation. In particular, the morphological characters of RA spine synaptic contacts between 2 major pathways were altered differently. However, experimental disruption of the basal ganglia circuit, through lesions in song-specialized basal ganglia nucleus Area X, largely prevented both the observed changes to RA dendritic spines and the song deterioration after hearing loss. Our results provide cellular evidence to highlight a key role of the basal ganglia circuit in the motor cortical plasticity that underlies learned vocal plasticity.

Effect of l-Arginine in One Patient with Peroxisome Biogenesis Disorder due to PEX12 Deficiency.

Peroxisome biogenesis disorders (PBD) are a heterogeneous group of disorders due to PEX genes mutations, with a broad clinical spectrum comprising severe neonatal disease to mild presentation. Recently, Berendse et al reported an improvement of peroxisomal functions with l-arginine supplementation in fibroblasts with specific mutations of PEX1, PEX6, and PEX12. We report the first treatment by l-arginine in a patient homozygous for the specific PEX12 mutation shown to be l-arginine responsive in fibroblasts. We described the effect of l-arginine on biochemical (decrease of some plasma peroxisomal parameters) and neurophysiological (improvement of deafness) parameters. Some subjective clinical effects have also been observed (no more sialorrhea, behavior improvement). More studies are needed to assess the efficacy of l-arginine in some PBD patients with specific mutations.

Concurrent chemoradiotherapy was associated with a higher severe late toxicity rate in nasopharyngeal carcinoma patients compared with radiotherapy alone: a meta-analysis based on randomized controlled trials.

BACKGROUND: To investigate the incidence and risk of severe late toxicity with concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma patients. METHODS: Eligible studies included prospective randomized controlled trials (RCTs) evaluating CCRT versus radiotherapy alone in patients with nasopharyngeal carcinoma and in which data on severe late toxicities were available. Random effects or fixed effect models were applied to obtain the summary incidence, relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Five RCTs with 1102 patients with NPC were included in this analysis. The summary incidence of overall severe late toxicities in patients receiving CCRT was 30.7% (95% CI, 18-47.2%) and the incidence of radiotherapy alone group was 21.7% (95% CI, 13.3-33.4%). The use of concurrent chemotherapy was associated with an increased risk of severe late toxicities, with a RR of 1.349 (95% CI, 1.108-1.643; P = 0.005). As for specific late toxicity, CCRT significantly increased the risk of ear deafness/otitis (RR = 1.567; 95% CI, 1.192-2.052), but other late toxicities were not significantly different. Patients receiving concurrent chemotherapy regimens with 3-week high-dose cisplatin (HC) have a higher risk of ear deafness/otitis (RR = 1.672; 95% CI, 1.174-2.382; P = 0.026). However, there was no significant increase in the RR of severe ear complication with the addition of non-3-week high-dose cisplatin (nonHC) regimens (RR = 1.433; 95% CI, 0.946-2.171; P = 0.095). CONCLUSION: With the present evidence, the addition of concurrent chemotherapy seems to increase the risk of severe late toxicities in patients with NPC, especially when using HC regimen for the occurrence of severe ototoxicity.

Deafness in cochlear and auditory nerve disorders.

Sensorineural hearing loss is the most common type of hearing impairment worldwide. It arises as a consequence of damage to the cochlea or auditory nerve, and several structures are often affected simultaneously. There are many causes, including genetic mutations affecting the structures of the inner ear, and environmental insults such as noise, ototoxic substances, and hypoxia. The prevalence increases dramatically with age. Clinical diagnosis is most commonly accomplished by measuring detection thresholds and comparing these to normative values to determine the degree of hearing loss. In addition to causing insensitivity to weak sounds, sensorineural hearing loss has a number of adverse perceptual consequences, including loudness recruitment, poor perception of pitch and auditory space, and difficulty understanding speech, particularly in the presence of background noise. The condition is usually incurable; treatment focuses on restoring the audibility of sounds made inaudible by hearing loss using either hearing aids or cochlear implants.

Effect of hypoglycemic anti-deafness capsules in diabetic patients with deafness and toxicological assessment in rats.

OBJECTIVE: Through experiment on animals and clinical trials to explore the safety and efficacy of hypoglycemic anti-deafness capsules on diabetic patients with deafness. METHODS: Total 296 patients with non-insulin dependent diabetes mellitus (NIDDM) were randomly divided into two groups. A treatment group of 164 patients (208 ears) was treated with hypoglycemic anti-deafness capsules based on TCM syndrome differentiation. A control group of 132 patients (184 ears) was treated with glibenclamide and conventional drug treatment for deafness. The following were observed: hearing, fasting plasma glucose (FPG), 2 h postprandial plasma glucose (2hPG), 24 h urine glucose (24hUG), improvement of main symptoms, platelet function, and changes in superoxide dismutase (SOD) and lipid peroxide (LPO) levels. In animal studies, Kunming mice, weighing 18-22 g were used. Half of the mice were males and half were females. Wistar rats, weighing 80-120 g were used. Half of the rats were males and half were females. Male Wistar rats, weighing 200-220 g, were also used. Their acute and chronic toxicity was studied. RESULTS: The hearing improvement was 56.7% in the treatment group and 26.6% in the control group. FPG, 2hPG, and 24hUG were improved significantly (P < 0.05, P < 0.01, P < 0.01, respectively) in the treatment group and 2hPG and 24hUG improved significantly in the control group (P < 0.05, P < 0.05). The improvement in 2hPG and 24hUG in the treatment group was significantly greater than that in the control group P < 0.01).There was no significant difference in FPG between the two groups (P < 0.05). Main symptoms in the treatment group were significantly more improved than those in the control group (P < 0.05, P < 0.01). In the treatment group, platelet adhesion and aggregation, SOD, and LPO were all significantly improved from before treatment (P < 0.05, P < 0.01). However, in the control group, except LOP (P < 0.05), there were no significant differences from before treatment to after (P < 0.05). In animal studies, no obvious acute or long-term toxicity was observed from capsule administration. CONCLUSION: Through experiment on animals and clinical trials, we can found that hypoglycemic anti-deafness capsules could decrease blood glucose and serum triglycerides of alloxan-induced diabetic rats. This herbal capsule is effective for safely treating diabetic patients with deafness.

Incomplete cochlear partition type II variants as an indicator of congenital partial deafness: a first report.

INTRODUCTION: The increased understanding on the impact of partial deafness (PD) with residual low-frequency hearing has led to new hearing rehabilitation strategies using hearing preservation techniques during cochlear implantation with the aim to make use of the combined electric acoustic stimulation (EAS) in the affected ear. As a first report, we describe minor forms of the incomplete cochlear partition type II (IP- II) involving the apical 1.5 turns, which were found in the majority of our patients presenting with congenital PD. We investigated the hearing preservation rates and hearing outcomes of these patients after EAS cochlear implantation (EAS-CI). MATERIALS AND METHODS: We present a review of a case series of 4 children and 1 adult with documented congenital PD. They all underwent audiologic and radiologic assessment for CI. Hearing preservation rates and speech perception outcomes were assessed at 1, 3, 6, 12, and 24 months after EAS-CI. RESULTS: Three (75%) of the 4 pediatric patients and 1 adult patient with congenital PD showed the pattern of isolated IP-II variants involving the apical 1.5 cochlear turns with a normal basal turn, without associated inner ear anomalies. Complete hearing was preserved in all patients. Speech performance improved significantly in all patients. CONCLUSION: As a first report, we describe minor IP-II variants identified in the majority of our patients with congenital PD; these IP-II variants could be useful as an indicator of malformation for congenital PD. Detection requires careful radiologic evaluation of the cochlea. EAS-CI is not a contraindication in these patients and should be considered early to prevent permanent speech and language deficits.

Recovery from forward masking in elderly cochlear implant users.

OBJECTIVE: To compare temporal aspects of peripheral neural responses and central auditory perception between groups of younger adult and elderly cochlear implant users. STUDY DESIGN: Cohort study. SETTING: Academic hospital and cochlear implant center. PATIENTS: Adult cochlear implant users aged 28 to 57 years in the younger group (n = 5) and 61 to 89 years (n = 9) in the elderly group. All subjects used Advanced Bionics devices. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Time constants of neural (i.e., electrically evoked compound action potentials [ECAPs]) and perceptual recovery from forward masking. Interstimulus intervals (ISIs) were varied in both experiments. RESULTS: ECAP recovery rates were equivalent between groups, and no correlation was found between ECAP recovery and age. No correlations were found between ECAP recovery and speech perception. Psychophysical recovery was significantly slower in the elderly compared with the younger subjects (p < 0.0005), with a significant effect of age (R2 = 0.70, p < 0.0005). At the longest ISI (240 ms), elderly subjects experienced a mean maximum threshold shift of 35.2% (relative to 1 ms ISI) versus 14.8% for younger subjects. There was a significant positive relationship between psychophysical recovery and consonant-nucleus-consonant word scores (R2 = 0.62, p < 0.001), although no relationship was found with Hearing in Noise Test sentences. CONCLUSION: These findings suggest that difficulties observed in speech perception by elderly CI users may be due to age-related changes in the central rather than peripheral auditory system. With further study, these results may provide information to allow clinicians to assess patients' temporal processing abilities and facilitate setting program parameters that will maximize their auditory perceptual experience with a cochlear implant.

The Fickle finger of quackery in otology: the saga of Curtis H. Muncie, Osteopath.

OBJECTIVE: Throughout history, false and outrageous cures for deafness have been abundant. Most of these false remedies were short lived and did not gain much attention. However, Curtis H. Muncie, a New York osteopathic physician, accrued vast wealth and fame over a half century career (1910-1960) with his proclaimed cure of deafness through reconstruction of the Eustachian tube with his index finger. Through creative marketing, clever manipulation of the press, and outrageous claims of efficacy, he profited handsomely from what was, no doubt, the most egregious and remunerative instance of deafness quackery in 20th century otology. DATA SOURCES: A collection of original pamphlets issued by Curtis H. Muncie between 1921 and 1960 supplemented by articles from the popular press and both osteopathic and medical journals. RESULTS: The evidence that Dr. Muncie used unscientific methods and unscrupulous business practices is overwhelming. Famously, he fraudulently claimed in 1923 and for years thereafter that he had cured a congenitally deaf Spanish Prince (Don Jaime). At the height of the depression, his magical finger earned him over half a million dollars. Even his 1942 prison sentence for tax evasion did not keep him from resuming his flimflam upon his release. CONCLUSION: The story of Curtis H. Muncie is the quintessential example of how desperate patients can be exploited by an unscrupulous practitioner whose goal is satisfying his own avarice rather than curing illness.

Simultaneous grouping in cochlear implant listeners: can abrupt changes in level be used to segregate components from a complex tone?

A sudden increase in the amplitude of a component often causes its segregation from a complex tone, and shorter rise times enhance this effect. We explored whether this also occurs in implant listeners (n = 8). Condition 1 used a 3.5-s "complex tone" comprising concurrent stimulation on five electrodes distributed across the array of the Nucleus CI24 implant. For each listener, the baseline stimulus level on each electrode was set at 50% of the dynamic range (DR). Two 1-s increments of 12.5%, 25%, or 50% DR were introduced in succession on adjacent electrodes within the "inner" three of those activated. Both increments had rise and fall times of 30 and 970 ms or vice versa. Listeners reported which increment was higher in pitch. Some listeners performed above chance for all increment sizes, but only for 50% increments did all listeners perform above chance. No significant effect of rise time was found. Condition 2 replaced amplitude increments with decrements. Only three listeners performed above chance even for 50% decrements. One exceptional listener performed well for 50% decrements with fall and rise times of 970 and 30 ms but around chance for fall and rise times of 30 and 970 ms, indicating successful discrimination based on a sudden rise back to baseline stimulation. Overall, the results suggest that implant listeners can use amplitude changes against a constant background to pick out components from a complex, but generally these must be large compared with those required in normal hearing. For increments, performance depended mainly on above-baseline stimulation of the target electrodes, not rise time. With one exception, performance for decrements was typically very poor.

Transtympanic electrical stimulation for immediate and long-term tinnitus suppression.

Tinnitus is a common symptom which often becomes disabling, affecting the emotional and psychosocial dimensions of life. There are many reports describing tinnitus suppression or attenuation through electrical stimulation of the ear, provided either by cochlear implants or by transtympanic stimulation. Our study project aims to assess the effects of electrical promontory stimulation (EPS) on persistent disabling tinnitus. We enrolled 11 patients affected by postlingual monoaural or binaural profound hearing loss and disabling tinnitus in the worse ear. EPS was performed with direct continuous positive current delivered by an active platinum-iridium needle electrode connected to a promontory stimulator device. The short-term effect on tinnitus was assessed during and immediately after the stimulation. Long-term effects were estimated after one month by comparing pre- and post-EPS Tinnitus Handicap Inventory (THI) scores. Immediately after EPS, five patients (45.4%) reported complete suppression and four (36.4%) reported attenuation of tinnitus. Two patients (18.2%) said it was unchanged. After one month, the THI score was reduced in five patients (45.4%) and remained unchanged in the other six patients (54.6%). The beneficial effects of EPS on tinnitus might be explained by interference with tinnitus generating circuits such as the dorsal cochlear nucleus and the inferior colliculus and by modification of cortical activity. EPS is to be considered a worthwhile attempt at tinnitus suppression, and could help select candidates for the positioning of an implantable electrical stimulator that might provide longer-term beneficial effect on tinnitus.

Neurodevelopmental outcomes of premature infants treated with l-arginine for prevention of necrotising enterocolitis.

AIM: This study aimed to compare the long-term neurodevelopmental outcomes at 36 months adjusted age in preterm infants (birth weight < or = 1250 gm) who received supplementation with L-arginine during the first 28 days of life with controls. METHODS: Surviving infants enrolled in a randomised control study of L-arginine supplementation were prospectively followed longitudinally to determine their neurodevelopmental outcomes at 36 months of adjusted age. Neurologic examination and neurodevelopmental assessments were performed by examiners who were unaware of the original treatment assignments. RESULTS: A total of 132 children (95% of survivors) were evaluated at 36 months adjusted age. In the group given L-arginine, 5 of 61 (8.1%) had major neurodevelopmental disabilities, defined as the presence of one or more of cerebral palsy, cognitive delay (cognitive index <70), bilateral blindness or bilateral hearing loss requiring hearing aids as compared with 9 of 71 (12.6%) in the placebo group (relative risk, 0.64; 95 % confidence interval, 0.22-1.82; P= 0.40). CONCLUSIONS: There is no increase in neurodevelopmental disability in preterm infants who received L-arginine supplementation.

Anakinra improves sensory deafness in a Japanese patient with Muckle-Wells syndrome, possibly by inhibiting the cryopyrin inflammasome.

Muckle-Wells syndrome (MWS) is a dominantly inherited autoinflammatory syndrome. Patients with MWS have a mutation in CIAS1, the gene encoding cryopyrin, a component of the inflammasome that regulates the processing of interleukin-1beta (IL-1beta). In this report we describe an 8-year-old Japanese girl with MWS who had symptoms of periodic fever, urticarial rash, conjunctivitis, arthropathy, and sensory deafness. Laboratory analysis of the patient's serum showed abnormally high concentrations of C-reactive protein, serum amyloid A, and IL-1beta, and she had a heterozygous mutation in the CIAS1 gene, with C-to-T transversion at nucleotide position 778, encoding an arginine-to-tryptophan mutation at position 260 (R260W). Mononuclear cells (MNCs) isolated from the patient secreted large amounts of IL-1beta, without stimulation, and were highly sensitive to muramyldipeptide and lipopolysaccharide. After treatment with anakinra, laboratory results normalized, and clinical symptoms, including sensory deafness, disappeared, while MNCs appeared to remain activated. Thus, our case suggests that anakinra possibly affects the cryopyrin inflammasome and markedly improves the clinical and laboratory manifestations of MWS.

Thiamine-responsive megaloblastic anaemia syndrome: long-term follow-up and mutation analysis of seven families.

AIM: Thiamine-responsive megaloblastic anaemia syndrome (TRMA) is the association of diabetes mellitus, anaemia and deafness, due to mutations in SLC19A2, encoding a thiamine transporter protein. This is a unique monogenic form of vitamin-dependent diabetes for which there is limited long-term data. We aimed to study genotype-phenotype relationships and long-term follow-up in our cohort. METHODS: We have studied 13 patients from seven families and have follow-up data for a median of 9 y (2-30 y). RESULTS: All patients originated from Kashmir or Punjab, and presented with non-immune, insulin-deficient diabetes mellitus, sensorineural deafness and a variable anaemia in the first 5 y of life, the anaemia progressing to megaloblastic and sideroblastic changes in the bone marrow. The anaemia and diabetes mellitus responded to oral thiamine hydrochloride 25 mg/d, but during puberty thiamine supplements became ineffective, and almost all patients require insulin therapy and regular blood transfusions in adulthood. All patients are homozygous for mutations in the SLC19A2 gene. We have identified a novel missense mutation (T158R) that was excluded in 100 control alleles. CONCLUSION: Diabetes in this syndrome is due to an insulin insufficiency that initially responds to thiamine supplements; however, most patients become fully insulin dependent after puberty. A mutation screening strategy is feasible and likely to identify mutations in almost all cases.

Electrical stimulation levels and electrode impedance values in children using the Med-El Combi 40+ cochlear implant: a one year follow-up.

The present study was designed to follow changes in electrical stimulation levels and electrode impedance values (EIV) in children using the Med-El Combi 40+ cochlear implant (CI) during the first 12 months of implant use. The maps of 24 prelingually deaf children implanted at a mean age of 5.9 years (range 1-15.9 years) using the TEMPO+ speech processor programmed with CIS+ strategy were examined at five time points: initial stimulation, and 1, 3, 6, and 12 months post-initial stimulation. Most comfortable levels (M) and electrode impedance values (EIV) were analyzed according to three cochlear segments: apical, medial, and basal. Results indicated a significant increase in M levels until the 3-month time point, thereafter stabilization was evident. Furthermore, M levels in the apical segment were lower than those in the medial and basal segments. EIV decreased from initial stimulation to the 3-month time point and was then stable through the study follow up. Interestingly, the finding of higher EIV in the apical segment may be attributed to the physical characteristics of the Med-El electrode. In conclusion, the pattern of stabilization of M levels found in the present study is similar to that reported for children using other devices. The data presented here may be useful as a guideline for programming M levels and monitoring EIV in infants and young children. They may further help clinicians to identify those children that fall outside the 'typical' range.