Strategy for the surgical treatment of vestibular schwannomas in patients with neurofibromatosis type 2.

OBJECTIVE: Guidelines for appropriate management of vestibular schwannomas in NF2 patients are controversial. In this paper we reviewed our experience with patients with NF2 for the results of surgical treatment with particular reference to hearing and facial nerve preservation. METHODS: We included in the study 30 patients (16 women and 14 men) with the diagnosis of NF2 treated in our department between 1998 and 2014 who underwent surgery for vestibular schwannoma removal with a follow-up for at least 1 year. In 3 cases, the vestibular schwannomas were unilateral. Six patients with bilateral vestibular schwannomas underwent unilateral procedure. Therefore, 51 acoustic tumors were studied in 30 patients. RESULTS: No operative death we noted. Significant deterioration to the non-functional level occurred in 19 out of 22 cases with well-preserved preoperative hearing. Only three ears maintained their preoperative good hearing. Hearing was preserved in cases of small schwannoma not exceeding 2 cm. Among 21 patients who underwent bilateral operations hearing was preserved in 3 out of 7 cases when smaller tumor or better hearing level side was attempted at first surgery. In contrary none of the 14 patients retained hearing when the first operation concerned the worse-hearing ear. Among 14 tumors up to 2 cm there was only one case of moderately severe facial nerve dysfunction (House-Brackmann Grade IV) in the long follow-up. CONCLUSION: Early surgical intervention for vestibular schwannoma in NF2 patient is a viable management strategy to maintain hearing function and preserve facial nerve function.

[Possibility of hearing preservation treatment by patient suffered from neurofibromatosis type 2: case report]. / Mozliwosci zachowania sluchu u pacjenta z neurofibromatoza typu 2--opis przypadku.

The main tumor of cerebellopontine angle are vestibular schwannoma (80-90%). Most of them are unilateral lesion but 5% of them are bilateral pathological mass. There are genetic disease like neurofibromatosis type 1 and 2. According to National Institute of Heath Consensus Development Conference the best treatment method is microsurgery. The possibility of hearing preservation surgery give middle fossa approach and suboccipital approach, radiotherapy or auditory brainstem implants and cochlear implants. The aim of the study is case report of the patient suffered from bilateral vestibular schwannoma. Early diagnosis and therapy enable hearing preservation and good facial nerve function.

Hearing preservation after stereotactic radiosurgery for bilateral cerebellopontine angle meningiomas.

BACKGROUND: Preservation of cranial nerve function is critical in the management of patients with cerebellopontine angle (CPA) tumors. CASE REPORT: A 51-year-old woman with tinnitus and dizziness was discovered to have bilateral CPA dural-based masses extending into the internal auditory canals (IAC). Pre-operatively, the patient had normal hearing on the right (SRT, 5 dB; SDS 100% at 30 dB) and left (SRT, 10 dB; SDS 90% at 40 dB). The patient underwent two Leksell Gamma Knife (Elekta Instruments, Norcross, GA) radiosurgeries initially for the larger left-sided tumor, then one year later for the right. The margin dose for each tumor was 14 Gy. Six years after the first radiosurgery, the tumors have not progressed and she has retained normal hearing and facial function bilaterally. CONCLUSION: Preservation of cranial nerve function is generally possible after stereotactic radiosurgery of CPA meningiomas.

[Molecular mechanism of age-related hearing loss: toward its prevention].

Mitochondrial DNA (mtDNA) mutations/deletions and decline of mitochondrial function are considered to be associated with the development of age-related hearing loss (AHL). First, we examined age-related changes in gene expression profile in the cochlea of DBA/2J mouse. This mouse exhibited mild hearing loss at 2 months of age and became deaf by 8 months. Comprehensive gene expression analysis identified significant expression changes correlated with AHL in over 4000 cochlear genes. When compared to 2 month old mice, approximately 2,200 genes were downregulated and approximately 1,900 genes were upregulated in the cochlea of 8 month old mice. AHL-correlated genes in the cochlea of 8-month-old DBA/2J mice were statistically associated with 15 mitochondrial process categories, suggesting that AHL is associated with profound down-regulation of genes involved in the mitochondrial function in the cochlea of aged DBA/2J mice. Next, we assessed the role of accumulation of mtDNA mutations in the development of AHL using Polg (D257A) knock-in mouse, which exhibited increased spontaneous mtDNA mutation rates during aging and showed accelerated aging. They exhibited moderate hearing loss and degeneration and apoptosis in the cochlea by 9 month of age, while wild-type animals did not. MtDNA mutations were associated with transcriptional alterations consistent with impairment of energy metabolism, induction of apoptosis, and hearing dysfunction in the cochlea of aged mitochondrial mutator mice. Lastly, we examined if 26% calorie restriction (CR) could prevent AHL in C57BL/6 mice. CR mice retained normal hearing and showed no cochlear degeneration by 15 months of age, whereas control mice developed moderate hearing loss and cochlear degeneration due to increased apoptosis at 15 months of age. CR mice also showed a significant reduction in the number of TUNEL-positive cells and cleaved caspase-3-positive cells. Microarray analysis revealed that CR upregulated the expression of genes involved in mitochondrial and hearing function and downregulated that of apoptotic genes. Taken together, these findings suggest that accumulation of mtDNA mutations during aging leads to mitochondrial dysfunction and induces an apoptotic program, thereby causing AHL.

l-Thyroxine does not prevent immunemediated sensorineural hearing loss in autoimmune thyroid diseases.

OBJECTIVE: This is the first report dealing with immune-mediated inner ear disease (IMIED) hearing loss in a group of patients affected with autoimmune thyroid disease (AITD), whose treatment required corticosteroids, despite being treated with levothyroxine. Immunopathology linking the inner ear and the thyroid gland is also presented. PATIENTS: A total of 220 patients were selected with sensorineural hearing loss (SNHL) of causes other than presbycusis. Audiometry was performed and pure tone average was calculated before and after treatment with corticosteroids. RESULTS: Eighty-four (84) patients had SNHL of autoimmune origin, and 15 patients were diagnosed with AITD (Hashimoto's disease). Bilateral hearing loss was observed in 10 patients (66.5%). Sudden sensorineural hearing loss was the most frequent clinical form of presentation. Nine patients showed a hearing recovery greater than 10dB after corticosteroid treatment. CONCLUSIONS: Acquired hypothyroidism is thought to affect hearing due to different mechanisms. Although specific hormonal therapy may improve peripheral or central auditory disorders associated with hypothyroidism, the presence of IMIED in AITD patients requires another approach. Altered immune regulatory mechanisms involving Treg cells and CD4+CD45RO cells have been suggested in patients with AITD and IMIED. In the present study, although all the patients with hypothyroidism and subclinical hypothyroidism were being treated with levothyroxine, immune-mediated hearing loss was observed. Therapy with corticosteroids could achieve hearing recovery. Since inner ear and thyroid gland share possible antigen targets, we highlight the existence of IMIED in AITD patients and the importance of implementing appropriate therapy with corticosteroids.

Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide.

BACKGROUND: Chronic lung disease and severe intraventricular hemorrhage or periventricular leukomalacia in premature infants are associated with abnormal neurodevelopmental outcomes. In a previous randomized, controlled, single-center trial of premature infants with the respiratory distress syndrome, inhaled nitric oxide decreased the risk of death or chronic lung disease as well as severe intraventricular hemorrhage and periventricular leukomalacia. We hypothesized that infants treated with inhaled nitric oxide would also have improved neurodevelopmental outcomes. METHODS: We conducted a prospective, longitudinal follow-up study of premature infants who had received inhaled nitric oxide or placebo to investigate neurodevelopmental outcomes at two years of corrected age. Neurologic examination, neurodevelopmental assessment, and anthropometric measurements were made by examiners who were unaware of the children's original treatment assignment. RESULTS: A total of 138 children (82 percent of survivors) were evaluated. In the group given inhaled nitric oxide, 17 of 70 children (24 percent) had abnormal neurodevelopmental outcomes, defined as either disability (cerebral palsy, bilateral blindness, or bilateral hearing loss) or delay (no disability, but one score of less than 70 on the Bayley Scales of Infant Development II), as compared with 31 of 68 children (46 percent) in the placebo group (relative risk, 0.53; 95 percent confidence interval, 0.33 to 0.87; P=0.01). This effect persisted after adjustment for birth weight and sex, as well as for the presence or absence of chronic lung disease and severe intraventricular hemorrhage or periventricular leukomalacia. The improvement in neurodevelopmental outcome in the group given inhaled nitric oxide was primarily due to a 47 percent decrease in the risk of cognitive impairment (defined by a score of less than 70 on the Bayley Mental Developmental Index) (P=0.03). CONCLUSIONS: Premature infants treated with inhaled nitric oxide have improved neurodevelopmental outcomes at two years of age.

Unaided and aided performance with a directional open-fit hearing aid.

Differences in performance between unaided and aided performance (omnidirectional and directional) were measured using an open-fit behind-the-ear (BTE) hearing aid. Twenty-six subjects without prior experience with amplification were fitted bilaterally using the manufacturer's recommended procedure. After wearing the hearing aids for one week, the fitting parameters were fine-tuned, based on subjective comments. Four weeks later, differences in performance between unaided and aided (omnidirectional and directional) were assessed by measuring reception thresholds for sentences (RTS in dB), using HINT sentences presented at 0 degrees with R-Space restaurant noise held constant at 65dBA and presented via eight loudspeakers set 45 degrees apart. In addition, the APHAB was administered to assess subjective impressions of the experimental aid. Results revealed that significant differences in RTS (in dB) were present between directional and omnidirectional performance, as well as directional and unaided performance. Aided omnidirectional performance, however, was not significantly different from unaided performance. These findings suggest for the hearing aids and experimental condition used in this study, a patient would require directional microphones in order to perform significantly better than unaided or aided with omnidirectional microphones, and that performance with an omnidirectional microphone would not be significantly better than unaided. Finally, the APHAB-aided scores were significantly better than unaided scores for the EC, BN, RV, and AV subscales indicating the subjects, on average, perceived the experimental aid to provide significantly better performance than unaided, and that aided performance was more aversive than unaided.

The protective effect of intratympanic dexamethasone on cisplatin-induced ototoxicity in guinea pigs.

OBJECTIVE: The purpose of this study was to investigate the effectiveness of intratympanic dexamethasone injection as a protection agent against cisplatin-induced ototoxicity. STUDY DESIGN AND SETTING: The four groups of guinea pigs were injected as follows: 1) cisplatin, 2) intratympanic dexamethasone, 3) cisplatin following intratympanic dexamethasone, and 4) cisplatin after intratympanic saline. Before and 3 days following injections, the ototoxic effect was measured with distortion product otoacoustic emissions (DPOAEs). RESULTS: The DPOAEs amplitudes and signal-to-noise ratio (SNR) values at 1 to 6 kHz frequencies for group 1 animals after injections significantly decreased over those before injections (P < 0.05). In group 2, there were no significant differences in DPOAE amplitude and SNR values between before and after intratympanic dexamethasone injections (P > 0.05). Considering group 3, there were also no significant differences in DPOAEs amplitudes and SNR values before and after of dexamethasone and cisplatin injections (P > 0.05). CONCLUSIONS: Intratympanic dexamethasone injection did not cause any ototoxic effect; in contrast, it might have a significant protective effect after cisplatin injection.

Infant hearing screening at immunization clinics in South Africa.

OBJECTIVE: Benefits of early identification and subsequent intervention for hearing loss are not accessible to infants in developing countries like South Africa. There are no systematic screening programs and traditional platforms for newborn hearing screening, such as well-baby and intensive care nurseries, do not provide sufficient coverage due to the high incidence of births at home or in primary healthcare facilities. Primary healthcare structures, in the form of immunization clinics, have been proposed as an alternative screening platform. The current study, therefore, investigates a hearing screening program implemented at two immunization clinics in a representative South African community. METHODS: The two clinics in the current study were selected by a convenience sampling method in a community representative of large sections of the population. The hearing screening program was conducted over a 5-month period, and enrolled 510 infants (0-12 months of age). The screening protocol included Distortion Product Oto-Acoustic Emissions (DPOAE) and a high frequency probe tone (1000 Hz) tympanogram. Referral was based on one or both ears referring the DPOAE screen. Follow-up screening and diagnostic evaluations were scheduled for referred subjects. RESULTS: Coverage with DPOAE amounted to 95% of the sample ears (93% of sample subjects) compared to tympanogram coverage amounting to 94% (93% of sample subjects). OAE pass rates were 93% for the sample ears with neonatal ears indicating a higher pass rate of 95% compared to 92% for infant ears (5-52 weeks of age). Eighty-seven percent of the sample ears indicated peaked tympanograms indicative of normal middle-ear functioning and neonatal ears presented with an increased incidence of peaked tympanograms (92%). A highly significant association between the DPOAE and high frequency tympanometric result was found. Follow-up screening appointments were scheduled for 68 subjects (14% of screened sample). Only 40% returned for the second follow-up and 44% for the third follow-up. CONCLUSIONS: Immunization clinics indicate promise as infant hearing screening platforms, but identification of only bilateral hearing losses may be warranted initially to keep referral rates acceptably low. In addition to this efficient tracking systems are necessary to ensure acceptably high follow-up return rates are reached over time.

[Hearing screening in infants with congenital cytomegalovirus infection].

OBJECTIVE: To investigate the impact of congenital cytomegalovirus infection on the hearing ability in infants. METHODS: By using the tools of distortion product otoacoustic emission (DPOAE) and auditory brain-stem response (ABR), the hearing ability of 38 infants with congenital cytomegalovirus infection and 16 cases of normal controls during neonatal periods was screened with a follow-up study at 6 and 24 months. RESULT: In infants with congenital cytomegalovirus infection, 86.8% (66/76) ears at neonatal stage and 76.3% (58/76) ears at 6 months passed the tests; while in normal controls, 96.9% (31/32) ears passed the tests. The reaction threshold of ABR V in infants with congenital cytomegalovirus infection was higher than that in normal controls (P<0.005). Furthermore,in infants with congenital cytomegalovirus infection, 13 ears (17.1%) were extreme hearing loss, 5 ears (6.6%) were severe hearing loss, and 6 ears (7.9%) were moderately severe hearing loss. The incidence of hearing loss during the follow-up was 7.9% (3/38) at neonatal stage, 23.7% (9/38) at 3-4 months, and 7.9% (3/38) after 6 months. CONCLUSION: The congenital cytomegalovirus infection could cause the prompt and late-onset hearing loss. The combination of the laboratory evidence with the dynamic hearing screening may contribute to the early detection of hearing loss in infants with congenital cytomegalovirus infection.

Neurotrophic and antioxidant effects of silymarin comparable to 4-methylcatechol in protection against gentamicin-induced ototoxicity in guinea pigs.

BACKGROUND: Despite that gentamicin is a very effective aminoglycoside, its potential ototoxicity which is of irreversible nature makes a challenge and limitation for its use. This study was designed to investigate possible neurotrophic and antioxidant effects of silymarin comparable to 4-methylcatechol in protection against gentamicin-induced ototoxicity. METHODS AND RESULTS: Twenty pigmented guinea pigs were divided into four equal groups, where group I served as normal control group. The other groups received gentamicin (120 mg/kg/day, ip) for 19 days where group II given vehicle of 1% CMC, group III and group IV were pre-treated 2h before gentamicin by 4-methylcatechol (10 µg/kg, ip) and silymarin (100mg/kg, oral gavage), respectively. The main findings indicated that silymarin exhibited restoration of nerve growth factor (NGF) levels and increased tropomyosin-related kinase receptors-A (Trk-A) m-RNA expression in cochlear tissue and preservation of hair cells of organ of Corti by scanning electron microscopy (SEM) with significant decrease in auditory brainstem response (ABR) threshold compared to 4-methylcatechol. Only silymarin caused significant amelioration in oxidative stress state by reducing malondialdehyde (MDA) levels and increasing catalase activity. CONCLUSIONS: Silymarin exerts superiority over 4-methylcatechol when recommended as protective agent against gentamicin ototoxicity based on its efficient neurotrophic and antioxidant activities.

Clinical trials of nimodipine as a potential neuroprotector in ovarian cancer patients treated with cisplatin.

Our previous randomised trial in patients with advanced ovarian cancer indicated a significant response and survival advantage for those receiving high-dose (100 mg/m2) as compared with low-dose (50 mg/m2) cisplatin in combination with cyclophosphamide (750 mg/m2). However, this was accompanied by more toxicity; peripheral neuropathy was troublesome, with 32% of patients experiencing > or = WHO grade 2 at the cisplatin dose of 100 mg/m2. Nimodipine is a calcium-channel antagonist that has provided protection from cisplatin-induced neurotoxicity in a rat model system. We performed a pilot study in 50 patients that demonstrated the feasibility of co-administration of nimodipine in a chronic oral dosing schedule with cisplatin-based chemotherapy in an open-label non-randomised trial. This led us to initiate a double-blind, placebo-controlled, randomised trial in patients with ovarian cancer, which was prematurely discontinued because of problems with nausea and vomiting, leading to poor patient compliance, that were not predicted by the pilot study. These studies did not demonstrate a neuroprotective effect for nimodipine. The primary efficacy variable, i.e, the neurotoxicity score at the end of treatment, gave a significantly lower mean for placebo patients than for nimodipine patients. This report details our experience and discusses the reasons for premature termination of the randomised trial.

Short-duration space flight and hearing loss.

OBJECTIVES: The study goal was to determine whether a single Space Shuttle mission can induce decrements in astronaut hearing. Study design We retrospectively compared audiogram information obtained from Space Shuttle astronauts at 10 days preflight, day of return (R + 0), 3 days after landing return (R + 3), and at a mean delayed postflight follow-up of 8 months. RESULTS: Temporary threshold shift (mean, 4.6 dB) was noted in R + 0 versus preflight conditions (P < 0.01). Small permanent threshold shifts (mean, 0.83 dB) were found at R + 3 and postflight follow-up compared with preflight in the lower frequencies (500 to 2000 Hz), and corresponding pure tone average (P < 0.001). Conclusions and significance The data indicate that a single Shuttle flight can induce a substantial temporary threshold shift and a small but statistically significant permanent threshold shift, particularly in the frequencies involved in speech reception. Although single-mission effects are small, cumulative effects over several missions may ultimately produce clinically significant hearing loss.

The effects of etidronate disodium on progressive hearing loss from otosclerosis.

A 2-year prospective double-blind study was performed to evaluate the role of etidronate disodium for the treatment of progressive hearing loss in patients with otosclerosis. A pulsed dosage regimen was used during the 2-year period and the patients were followed up with otologic and audiometric examinations. Although statistically significant differences were not achieved between the study and control groups, the study did reveal a trend toward stabilization or improvement in air conduction thresholds in some frequencies (1000 and 4000 Hz) and in bone conduction thresholds at other frequencies (500, 1000, and 2000 Hz). The incidence of adverse side effects was similar in the treatment and control groups. Although no definite conclusions can be drawn from this pilot study, the findings provide encouragement for performing a larger and longer-term study.

Hearing preservation in acoustic neurinoma surgery.

In a series of 120 patients with acoustic neurinoma, hearing preservation at removal of the tumour via the suboccipital approach was attempted in 30 ears. Hearing was preserved in 13 ears (43%), but in two, hearing was lost entirely in 3 to 4 years; thus the success rate was 36%. In 9 of the remaining 11 ears useful speech discrimination was present. Audiological tests showed increased retrocochlear loss after surgery. A surgical team should master the methods of both translabyrinthine and suboccipital surgery in order to choose the best approach for each patient.

[Role of corticoids in purulent meningitis in children: analysis of literature studies]. / Place des corticoïdes dans les méningites purulentes de l'enfant: analyse des études de la littérature.

Steroid therapy, in combination with antibiotics for bacterial meningitis in paediatric patients remains controversial. Steroids, and primarily dexamethasone a very potent anti-inflammatory agent, regulate the liberation of various cytokines and inflammatory mediators such as prostaglandins, released during bacterial meningitis and leading to long term complications. Several clinical trials studying infants and children with bacterial meningitis due to Haemophilus influenzae have evaluated the beneficial effects of the administration of dexamethasone at the onset of antibiotherapy and demonstrated that dexamethasone reduced the risk of acquired sensorineural deafness (bilateral moderate or more severe hearing loss) and the incidence of neurological sequelae. Limited information is available for the other bacterial meningitis, although meningococcal meningitis will become more frequent with the use of effective anti-Haemophilus vaccines. In addition some Streptococcus pneumoniae are now resistant to third generation cephalosporins and the use of dexamethasone in that case may be at risk. Finally, no evidence is available for an effective role for dexamethasone in neonatal bacterial meningitis, although it is quite often administered in that age group.

[A rare case of the high jugular bulb associated with only hearing ear].

The jugular bulb may be present in different positions and dimensions within the temporal bone. In general, high jugular bulbs were classified into 2 types: lateral in which the jugular bulb protrudes into the middle ear and up into the tympanic cavity and medial in which the jugular bulb is abnormally placed more superiorly and medial to the cochlea. We report, a unique case of a high jugular bulb which came round from behind of the internal auditory canal and the cochlea protruding into the posterosuperior part of the mesotympanum. It was a very rare pattern of a high jugular bulb which varies in position. The occurrence of adhesive otitis media caused the high jugular bulb to bleed easily in the only hearing ear. There would be risks of making the patient suffer severe bilateral healing impairment due to only one hearing ear and excessive hemorrhage in surgical treatment. With only one hearing ear, we should therefore select transcatheter interventional angiography when the quantity and frequency of bleeding from the jugular bulb increase so.

[Incidence of coexisting sensorineural hearing loss and secretory otitis media]. / Czestosc wspólistnienia odbiorczego uszkodzenia sluchu i wysiekowego zapalenia ucha srodkowego.

There are currently no standard guidelines for assessing hearing in children who are evaluated for tympanostomy tubes. We describe the results of audiologic testing on 587 children, age 2 months to 17 years admitted to Pediatric Otolaryngology Department Bialystok for treatment of secretory otitis media. Ten children (1.7%) were found to have previously unrecognized sensorineural hearing loss. In four cases total unilateral deafness, in six others moderate to severe sensorineural bilateral hearing loss was diagnosed. Three other children referred to our clinic as sensorineural hearing loss were found to have secretory otitis media as the only or coexisting cause of deafness. Results of our study show the importance of age--appropriate hearing assessment as part of diagnostic procedure for secretory otitis media.