Patrice Tran Ba Huy

SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations

Sensorineural hearing loss is the most frequent sensory deficit of childhood and is of genetic origin in up to 75% of cases. It has been shown that mutations of the SLC26A4 (PDS) gene were involved in syndromic deafness characterized by congenital sensorineural hearing impairment and goitre (Pendreds syndrome), as well as in congenital isolated deafness (DFNB4). While the prevalence of SLC26A4 mutations in Pendreds syndrome is clearly established, it remains to be studied in large cohorts of patients with nonsyndromic deafness and detailed clinical informations. In this report, 109 patients from 100 unrelated families, aged from 1 to 32 years (median age: 10 years), with nonsyndromic deafness and enlarged vestibular aqueduct, were genotyped for SLC26A4 using DHPLC molecular screening and sequencing. In all, 91 allelic variants were observed in 100 unrelated families, of which 19 have never been reported. The prevalence of SLC26A4 mutations was 40% (40/100), with biallelic mutation in 24% (24/100), while six families were homozygous. All patients included in this series had documented deafness, associated with EVA and without any evidence of syndromic disease. Among patients with SLC26A4 biallelic mutations, deafness was more severe, fluctuated more than in patients with no mutation. In conclusion, the incidence of SLC26A4 mutations is high in patients with isolated deafness and enlarged vestibular aqueduct and could represent up to 4% of nonsyndromic hearing impairment. SLC26A4 could be the second most frequent gene implicated in nonsyndromic deafness after GJB2, in this Caucasian population.

Long‐term follow‐up of juvenile nasopharyngeal angiofibromas: Analysis of recurrences

Objectives: Juvenile nasopharyngeal angiofibroma often recurs if the tumor is large. This report is a long‐term follow‐up of these cases. It establishes the prognostic values of tumor extensions, analyzes the anatomic factors involved in recurrences, describes the spontaneous evolution of remnants based on a radiographic follow‐up, and evaluates the pertinence of complex combined surgical approaches for invasive tumors and the value of complementary endoscopy. Study Design: Retrospective review of 44 cases treated between 1985 and 1996. Methods: Statistical analysis of the correlation between recurrence and tumor extension as evaluated by systematic analysis of 18 putative tumor extensions on preoperative computed tomography scans. Results: Invasion of the skull base affected two‐thirds of the patients, and the rate of recurrence was 27.5%. Extensions to the infratemporal fossa, sphenoid sinus, base of pterygoids and clivus, the cavernous sinus (medial), foramen lacerum, and anterior fossa were correlated with more frequent recurrence. Long‐term radiographic follow‐up revealed putative residual disease in nine asymptomatic patients: these remnants gradually involuted. Conclusions: The data in the current study emphasize the prognostic value of skull base invasion and the difficulty of complete resection of extended lesions. Tumor remnants detected in symptom‐free patients should be kept under surveillance by repeated computed tomography scan, since involution may occur. Recurrent symptoms may be treated by radiotherapy (30 Gy) rather than by extended combined procedures. Endoscopic surgery should be combined with surgery for better control of skull base extensions.

Characterization of Mucosal Biofilms on Human Adenoid Tissues

Objectives: To demonstrate the presence of mucosal biofilm in adenoid tissue using double staining for visualization of both the bacterial matrix and the bacterial cells. To identify bacterial species present on the surface of the studied adenoids.

Vestibular evoked myogenic potentials in patients suffering from an unilateral acoustic neuroma: a study of 170 patients

OBJECTIVE To determine the value of investigating the vestibular evoked myogenic potentials (VEMPs) induced by clicks and 500 Hz short tone burst (STB) for the diagnosis of acoustic neuromas. METHODS We studied the average responses to 100dB clicks and 500 Hz STB in the ipsilateral sternomastoid muscle. Ninety-five healthy subjects and 170 patients suffering from a unilateral acoustic neuroma were included in that study. Caloric and audiometric tests results were also analyzed. RESULTS Thirty-six/170 patients (21.2%) exhibited normal responses to clicks and to STB whereas 134/170 (78.8%) gave abnormally low or no responses. 78/170 (45.9%) showed no responses to both clicks and STB. In 56/170 patients (32.9%), VEMPs induced by high level clicks and STB were discordant: STB VEMPs were either normal (n=32) or low (n=24) in patients with an abnormal response to clicks (no response n=40 or low response n=16). In contrast, STB-induced VEMPs were always normal in cases of normal responses to clicks. No strong, systematic correlation could be found between saccular nerve dysfunction and either the degree of 4-8 kHz hearing loss or the extent of horizontal canalar impairment. CONCLUSIONS These data indicate that high level clicks and STB provide complementary information about the functionality of the saccular nerve. Clicks are useful to detect a minor saccular nerve dysfunction. In cases in which there is no response to clicks, STB gives valuable information about a potential residual function of the saccular nerve.

Spontaneous Intracranial Hypotension: A Rare Cause of Labyrinthine Hydrops

Spontaneous intracranial hypotension should be considered as a possible cause of cochlear hydrops. We report a case of unilateral hearing loss attributed to spontaneous intracranial hypotension on the basis of characteristic abnormalities seen on magnetic resonance imaging. The diagnostic gold standards for intracranial hypotension are lumbar measurement of cerebrospinal fluid pressure and magnetic resonance imaging. The usual treatment is an autologous blood injection into the peridural spaces. The mechanism of hearing loss is thought to involve secondary perilymph depression due to a patent cochlear aqueduct. This perilymph depression would induce a compensatory expansion of the endolymphatic compartment, with a subsequent decrease in basilar or Reissners membrane compliance. Endolymphatic hydrops can occur in the course of intracranial hypotension, and not only because of abnormal endolymph production or resorption. Hydrops can thus be classified into 1) syndromes of endolymphatic origin and 2) syndromes of perilymphatic origin, in which loss of perilymph induces compensatory expansion of the endolymphatic space.

Aminoglycoside ototoxicity: influence of dosage regimen on drug uptake and correlation between membrane binding and some clinical features.

The influence of dosage regimen on gentamicin uptake by the inner ear tissues was investigated by radioimmunoassay in rat given single i.m. 10 or 100 mg/kg injection or i.v. 1.5 or 15 micrograms/min constant infusion. Results show that, for a given dose, discontinuous administration yields markedly lower tissue concentration than continuous administration and, thus, carries less ototoxic risk. Using 125I-labelled gentamicin as a radioligand correlation between membrane binding and clinical features was also studied in homogenates of organ of Corti and vestibular maculae of guinea-pig. Results show that: (i) as compared by Kd values, gentamicin exhibits a four-fold greater affinity for vestibule (Kd = 3 X 10(-7) M) than for cochlea (Kd = 1.2 X 10(-6) M). This explains the predilection of this antibiotic to affect the vestibular apparatus; (ii) the typical baso-lateral progression of ototoxic degeneration cannot be accounted for by a preferential uptake of the drug between base and apex.

Idiopathic sudden sensorineural hearing loss is not an otologic emergency.

Objective: To investigate whether delay in treatment has any influence on the audiometric outcome at Day 30 in idiopathic sudden sensorineural hearing loss. Study Design: Prospective study. Setting: Otorhinolaryngologic emergency center in Paris, France. Patients: Three hundred forty-seven consecutive cases of sudden sensorineural hearing loss were examined. A neurologic or retrocochlear cause was revealed in 17 cases. Four additional cases were lost for follow-up. Three hundred twenty-six cases of “idiopathic” sensorineural hearing loss seen within 7 days of onset were enrolled and classified by type according to five audiogram shapes: low tone (Type A), flat (Type B), high tone (Type C), cup-shaped (Type D) or total or subtotal (Type E). Because of loss for follow-up, the hearing outcome at 1 month could be evaluated in only 249 cases. Intervention: All 326 patients were given 1 mg/kg per day corticosteroids intravenously for 6 days and 500 ml mannitol 10% in the subgroup presenting ascending audiometric shape. Main Outcome Measures: The following parameters were used. The first parameter was hearing recovery (initial PTA-PTA at Day 6 or Day 30). It was considered as complete if final PTA was below 25 dB. The second parameter was incidence of hearing recovery based on the following formula: (initial PTA-PTA on a given test day)/(initial PTA) × 100%. Using regression analysis and ANOVA, the audiometric outcome was analyzed at Day 6 and Day 30 as a function of the day of onset of treatment and of the audiometric type. Results: Whatever the audiometric type, there was no significant difference in final outcome whether the treatment was started within the first 24 hours or within the first week. Conclusions: Delay in initiating treatment does not appear to influence the final degree of hearing loss. Idiopathic sudden sensorineural hearing loss cannot be considered as an otologic emergency.

Transnasal endoscopic removal of an orbital cavernoma

The approach to posterior and medial orbital tumors is still a challenge, since poor functional results are frequent. We report a case of cavernoma successfully removed by a modified transnasal endoscopic procedure. The patient, a 56-year-old woman, complained of a decrease in vision of the left eye. Magnetic resonance imaging evidenced a lesion in the posterior part of the orbital cavity, inferior to the optic nerve, extending to the sphenoidal cleft. The lesion was isodense on T1-weighted images and showed contrast enhancement. Because of the medial location of the tumor, the patient was referred to the otolaryngology department by the neurosurgeons, and a transnasal endoscopic approach was chosen. A large exposure of the operative field was obtained, and a cavernoma was removed. Rapid relief of the symptoms was obtained. In view of this good result, we advocate the transnasal endoscopic approach in cases of inferomedial and posterior intraconal lesions as an alternative and addition to the standard techniques of orbital surgery.

A cationic nonselective stretch-activated channel in the Reissner's membrane of the guinea pig cochlea

The Reissners membrane (RM) separates in the mammalian cochlea the K(+)-rich endolymph from the Na(+)-rich perilymph. The patch-clamp technique was used to investigate the transport mechanisms in epithelial cells of RM freshly dissected from the guinea pig cochlea. This study shows a stretch-activated nonselective cationic channel (SA channel) with a linear current-voltage relationship (23 pS) highly selective for cations over anions [K+ approximately Na+ (1) > Ba2+ (0.65) > Ca2+ (0.32) >> Cl- (0.14)] and activated by the intrapipette gradient pressure. The open probability-pressure relationship is best fitted by a Boltzmann distribution (half-maximal pressure = 37.8 mmHg, slope constant = 8.2 mmHg). SA channels exhibit a strong voltage dependency and are insensitive to internal Ca2+, ATP, and fenamates but are blocked by 1 microM GdCl3 in the pipette. They are reversibly activated by in situ superfusion of the cell with hyposmotic solutions. Kinetic studies show that depolarization and mechanical or osmotic stretch modify the closed and open time constants probably by a different mechanism. These channels could participate in pressure-induced modifications of ionic permeability of the RM.

Mutations associated with succinate dehydrogenase D-related malignant paragangliomas.

Objective  Hereditary paraganglioma (PGL) syndromes result from germline mutations in genes encoding subunits B, C and D of the mitochondrial enzyme succinate dehydrogenase (SDHB, SDHC and SDHD). SDHB‐related PGLs are known in particular for their high malignant potential. Recently, however, malignant PGLs were also reported among a small minority of Dutch carriers of the SDHD founder mutation D92Y. The aim of the study was to investigate which SDHD mutations are associated with malignant PGL.