BACKGROUNDMyopathies with rimmed vacuoles are a heterogeneous group of muscle disorders with progressive muscle weakness and varied clinical manifestations but similar features in muscle biopsies. Here, we describe a novel autosomal dominant myopathy with rimmed vacuoles in a large family with 11 patients of three generations affected.

METHODSA clinical study including family history, obstetric, pediatric, and development history was recorded. Clinical examinations including physical examination, electromyography (EMG), serum creatine kinase (CK), bone X-rays, and brain magnetic resonance imaging (MRI) were performed in this family. Open muscle biopsies were performed on the proband and his mother. To find the causative gene, the whole-exome sequencing was carried out.

RESULTSDisease onset was from adolescence to adulthood, but the affected patients of the third generation presented an earlier onset and more severe clinical manifestations than the older generations. Clinical features were characterized as dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision. However, not every patient manifested all symptoms. Serum CK was mildly elevated and EMG indicated a myopathic pattern. Brain MRI showed cerebellum and brain stem mildly atrophy. Rimmed vacuoles and inclusion bodies were observed in muscle biopsy. The whole-exome sequencing was performed, but the causative gene has not been found.

CONCLUSIONSWe reported a novel autosomal dominant myopathy with rimmed vacuoles characterized by dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision, but the causative gene has not been found and needs further study.

Adolescent ; Adult ; Child ; Deafness ; diagnosis ; physiopathology ; Dysarthria ; diagnosis ; physiopathology ; Electromyography ; Female ; Humans ; Male ; Muscle Weakness ; diagnosis ; physiopathology ; Muscle, Skeletal ; pathology ; physiopathology ; Muscular Diseases ; diagnosis ; physiopathology ; Muscular Dystrophy, Oculopharyngeal ; diagnosis ; physiopathology ; Pedigree ; Vacuoles ; pathology ; Vision Disorders ; diagnosis ; physiopathology ; Young Adult

OBJECTIVETo establish a model of ototoxicity in guinea pigs with acoustically evoked short latency negative response (ASNR) and verify the responsible organ of ASNR based on microscopic characteristics of basal membranes, saccules, utricles and ampulla canalis semicircularis of the inner ear.

METHODSTotal of 45 guinea pigs were employed in the experiment, which were randomly divided into the control group (15 subjects, 30 ears) and the deafened group (30 subjects, 60 ears). Each animal experienced auditory brainstem response (ABR). A quick treatment was employed for deafened group consisting of a subcutaneous injection of kanamycin at a dose of 400 mg/kg followed by jugular vein injection of ethacrynic acid at a dose of 40 mg/kg one hour later. The animals were performed ABR test from 7 to 10 days after the drug administration. The deafened group was further divided into ASNR group and non-ASNR group based on the presence of ASNR. All the guinea pigs were sacrificed after ABR tests. The Corti organ, macula sacculi, macula utriculi and crista ampullaris were observed by light microscope.

RESULTSIn the deafened group (60 ears), 3 subjects died postoperatively, 27 subjects (54 ears) provided full data. ASNR was elicited in 19 ears (35.2%, 19/54), the thresholds of ASNR were from 110 to 125 dBSPL with average of (121.7 ± 4.5) dBSPL. ASNR latency ranges were 1.80 - 2.08 ms, the average latency of thresholds were (1.93 ± 0.07) ms. The stretched preparation results: overall hair-cell density of macula saccule, macula utriculi and crista ampullaris decreased in order of normal control group, ASNR group and non-ASNR group. There was no difference between the normal group and ASNR group for cell density of macula saccule. Apart from this, statistical differences were found among other groups.

CONCLUSIONSThe present study evoked ASNR in an ototoxicity guinea pig model which was profound hearing loss with normal saccular function and normal saccular hair cell density. It suggested that ASNR originates from the saccule and have no relation with cochlear, utricle and semicircular canal according to morphological study.

Acoustic Stimulation ; Animals ; Deafness ; physiopathology ; Ear, Inner ; physiopathology ; Evoked Potentials, Auditory ; Evoked Potentials, Auditory, Brain Stem ; Guinea Pigs ; Reaction Time ; Saccule and Utricle ; physiopathology

OBJECTIVE: To analyze the abnormal conditions of the affected ear and the contralateral ear of patients with unilateral Meniere's disease and the prevalence of bilateral abnormalities among these unilateral Meniere disease population, providing reference for the clinical treatment strategies for Meniére disease. METHOD: A retrospective analysis of 106 Meni6re disease cases was performed, the abnormal incidence of the affected ears, the contralateral ears and the bilateral abnormalities were calculated, and the disease characteristics were analyzed. RESULT: The bilateral ears abnormal incidence of unilateral Meniére disease was 35. 85% (38/106); the cochlear symptoms of the contralateral ears often occurred 2. 25 years later of the symptoms of Meni6re disease; contralateral cochlear symptoms included at least two symptoms of tinnitus, deafness and ear fullness; 39. 47%(15/38) patients with bilateral abnormalities would appear binaural hearing impairment. CONCLUSION This study showed that about one-third of unilateral Meniére diseases have binaural symptoms, among which about one-third would occur bilateral hearing loss. Therefore, it is necessary to consider the course of disease and the symptoms of the contralateral ear before taking damage or destructive method for treating Meniére's disease clinically.
Cochlea ; physiopathology ; Deafness ; Ear ; abnormalities ; Hearing Loss, Bilateral ; epidemiology ; Humans ; Incidence ; Meniere Disease ; epidemiology ; Prevalence ; Retrospective Studies ; Tinnitus

OBJECTIVETo conduct audiological assessment in patients with tympanosclerosis.

METHODSA retrospective review was conducted in 79 patients with tympanosclerosis (involving 79 ears) with complete records, including 30 patients (30 ears) with fixed Malleus-incus complex, 29 (29 ears) with fixed stapes, and 20 (20 ears) with fixations of both the stapes footplate and the Malleus-incus complex. Audiometry was performed for all the patients one or two days before operation, and the audiological features of the patients were compared between the 3 groups.

RESULTSMost of the patients (65.8%) suffered conductive hearing loss, 32.9% had mixed deafness, and one patient had sensorineural hearing loss. No statistically significant differences was noted in the speech frequency (0.5, 1, and 2 kHz) air conduction pure tone average (PTA) or the air-bone gap (ABG) in the 3 groups (P<0.05).

CONCLUSIONMost of the patients with tympanosclerosis suffer conductive hearing loss, and the severity of hearing loss is not associated with the site of tympanosclerosis.

Adolescent ; Adult ; Audiometry ; methods ; Deafness ; physiopathology ; Ear Diseases ; pathology ; physiopathology ; Female ; Hearing Loss, Conductive ; physiopathology ; Hearing Loss, Sensorineural ; physiopathology ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Sclerosis ; Tympanic Membrane ; pathology ; physiopathology ; Young Adult

OBJECTIVE: To evaluate the electrophysiological characteristics of electrically evoked auditory brainstem responses (EABR) and its application in cochlear implantation, especially in evaluating acoustic nerve survival. METHOD: An auditory evoked potential instrument was used to record responses and Cochlear Nucleus 24CA implants were used to generate electrical stimulation. We measured EABR in 23 patients with cochlear implants and compared EABR with behavioral measures and neural response telemetry (NRT). RESULT: EABR III-V waveforms were recognized in all of the 23 patients. The characteristics and origins of EABR waveforms were similar to those of ABR. The average EABR threshold was (172.61 +/- 14.61) CL. At 20 CL above threshold, the average latencies of Wave III, V were (2.93 +/- 0.18)ms, (4.80 +/- 0.28)ms which were 1-2 ms shorter than ABR latencies. But III-V intervals remained at (1.86 +/- 0.18)ms. EABR thresholds were strongly correlated with behavioral performance and NRT thresholds, while EABR input-output function is correlated with behavioral dynamic range (DR). CONCLUSION EABR is such an effective method to objectively evaluate the function of auditory pathway which can estimate residual spiral ganglion cell count. This is consistent with the foreign study leading to the conclusion that DR reflects spiral ganglion cell survival.
Auditory Threshold ; Child ; Child, Preschool ; Cochlear Implantation ; Cochlear Nerve ; physiopathology ; Deafness ; physiopathology ; surgery ; Evoked Potentials, Auditory, Brain Stem ; physiology ; Female ; Humans ; Infant ; Male

OBJECTIVE: L-type voltage-gated calcium channel subunit alpha1D-/- mice (homozygous mutant, knockout), alpha1D+/- (heterozygous) and alpha1D+/+ (wild-type) have played role in L-type voltage-gated calcium channel alpha1D subunit in auditory function of inner ear as well as sinoatrial node function of the mice. METHOD: Hearing threshold and endocochlear potential (EP) were measured in the alpha1D knockout mice, heterozygous mice and wild-type mice by auditory brainstem response(ABR), EP recordings and Electrocardiograph (ECG) respectively. To assessment of the vestibular function of the mice, the ability of Balancing was performed by a swim test and a horizontal cylinder test. RESULT: The auditory function of alD+/+ mice were normal, the mean value for ABR thresholds in response to click sound stimulus was (34.8 +/- 5.7) dB SPL,EP was (105.3 +/- 3.1) mV. The mean value for ABR thresholds in response to click sound stimulus was elevated in alpha1D+/- mice was (54.4 +/- 12.4) dB SPL, relative to that observed in alpha1D+/+ mice significantly increased (P < 0.05); EP of alpha1D+/- mice was about (75.8 +/- 9.9) mV. alpha1D-/- mice were completely deaf, the ABR wave form was not observed for even 100 dB SPL sound stimuli used and EP was still remain in (48.6 +/- 19.3) mV. alpha1D knockout mice were deaf and demonstrated no vestibular defect. alpha1D+/- and alpha1D-/- mice show significant sinus bradycardia with significant prolongation of the RR interval (146 +/- 1.4 and 244 +/- 2.9, respectively) comparing to the alpha1D+/+ wild-type mice (117 +/- 0.4) in the same littermates. In addition, the homozygous alpha1D-/- show a significant prolongation of the PR interval (53 +/- 0.5) compared to that of the a1D+/+ wild-type mice (38 +/- 0.3). CONCLUSION L-type voltage-gated calcium channel alpha1D subunit plays a critical role in calcium homeostasis in the inner ear. Mice lacking of alpha1D calcium channel gene would lead to influence auditory function and sinoatrial node dysfunction subsequently.
Animals ; Auditory Threshold ; Calcium Channels, L-Type ; genetics ; Deafness ; genetics ; physiopathology ; Electrocardiography ; Evoked Potentials, Auditory, Brain Stem ; Mice ; Mice, Knockout ; Sinoatrial Node ; physiopathology

OBJECTIVETo analyze the clinical characteristics, prognosis and therapeutic effects of sudden sensorineural hearing loss (SSHL) patients associated with vertigo, and to investigate the strategy of diagnosis and treatment.

METHODSWe retrospectively analyzed the clinical characteristics of 240 patients diagnosed as SSHL with vertigo, who were treated in the Chinese PLA General Hospital from July 2008 to August 2012. Various factors affecting the therapeutic effects were analyzed, such as audiological features, vestibular function tests, genders, audiograms, lasting before seeing a doctor, courses of vertigo and vascular factors.

RESULTAmong the contemporaneous SSHL patients (873 cases), the cases with vertigo accounted for 27.49% (240/873). Among the 240 patients with vertigo, the cases with different hearing impaired degree of mild, moderate, severe and profound were 30, 13, 28 and 34, respectively, primarily by the profound cases. Detailed vestibular function tests were performed in 97 patients, with 54 cases having unilateral vestibular disfunction and 43 patients having normal vestibular function, among which 23 cases were diagnosed as benign paroxymal positional vertigo (BBPV). The relationship between vestibular function and different hearing impaired degrees or various audiogram types had no statistically significant difference. 219 cases had detailed records of the onset time of cochlear and vestibular symptoms, including 122 patients with cochlear symptoms and dizziness occurring simultaneously. After standardized drug treatment, the total effective rate was 46.67%, with recovery in 17 cases, excellent in 34 cases, better in 61 cases and poor in 128 cases, respectively. Statistical analysis showed that different genders, audiogram types, vertigo courses of time, the results of vestibular function and neck vascular ultrasounds were not related to the curative effects, while, the treatment time after onset was significantly associated with treatment effects.

CONCLUSIONSSSHL with vertigo has a high incidence, primarily single side affected, with relatively severe hearing impairment, and total deafness and downslope hearing curve mainly. Vestibular function can be normal or low in SSHL patients with vertigo, with a higher incidence of BPPV. Vestibular and cochlear symptoms occur simultaneously in more than half of the patients. The detection rate of vestibular dysfunction gradually increased, as the degree of hearing loss increased, without statistical significance although. The therapeutic effects of sudden hearing loss with vertigo cases have no relationship with dizziness duration or vestibular function, while the disease course plays an important role in treatment.

Benign Paroxysmal Positional Vertigo ; complications ; Cochlea ; physiopathology ; Deafness ; Dizziness ; Hearing Loss, Sensorineural ; Hearing Loss, Sudden ; complications ; Hearing Tests ; Humans ; Prognosis ; Retrospective Studies ; Vestibular Function Tests ; Vestibule, Labyrinth ; physiopathology

OBJECTIVE: To explore the technique that distinguish pseudo-anacousia. METHODS: 60 cases were divided into three groups (normal group, deafness sensorineura group and pretending hearing loss group). They all had been tested by distortion products otoacoustic emissions technique. RESULTS: (1) The DPOAE incidence of normal group is 94.00%. the DPOAE incidence of deafness sensorineura group is 22.00%. There were significant differences at statistics in DPOAE incidence (P < 0.01). those proved that patients (deafness sensorineura group) were in hearing problem. (2) The DPOAE incidence of pretending hearing loss group is 93.00%, there were no significant differences at statistics in DPOAE incidence between normal group and pretending hearing loss group (P > 0.01), furthermore when behavior threshold is over 50 dBHL, DPOAE incidence is no score. CONCLUSION This study shows the technique can distinguish pretending hearing loss. The application of DPOAE can be used as a new tool in cases assessment of clinic forensic medicine.
Audiometry, Pure-Tone ; Auditory Threshold ; Deafness/physiopathology* ; Diagnosis, Differential ; Evoked Potentials, Auditory, Brain Stem ; Forensic Medicine ; Hearing Loss, Sensorineural/physiopathology* ; Humans ; Otoacoustic Emissions, Spontaneous

Abnormalities, Multiple ; diagnosis ; pathology ; physiopathology ; Branchio-Oto-Renal Syndrome ; diagnosis ; pathology ; physiopathology ; therapy ; Child ; Deafness ; etiology ; physiopathology ; Diagnosis, Differential ; Ear ; abnormalities ; Female ; Humans ; Kidney ; abnormalities ; Renal Insufficiency ; etiology ; physiopathology ; therapy

OBJECTIVETo investigate the clinical and genetic characteristics of three Chinese Meniere's disease (MD) families and decipher the mechanism of MD further.

METHODSPersonal and family medical evidence of hearing loss, vestibular symptoms, and other clinical abnormalities of the participants were identified, clinical and genetic features were analyzed. Targeted 307 genes capture and high-throughput sequencing were performed on the two ascertained members of family 1007184.

RESULTSEight patients from these three families showed post-lingual sensorineural hearing loss, six women and two men were involved. Age of onset in these affected members concentrated in the middle age, with the average age of 39.3 years old. Among them, patients from 1407278 were accompanied by migraine. All of the three probands presented as recurrent vertigo firstly, and then fluctuated hearing loss showed up, accompanying by tinnitus and ear fullness feeling. The hearing loss manifested as late-onset, low frequency-involved pattern, with subsequent gradual progression from moderate to severe level. Some of the patients progressed to severe level involving all frequencies at higher ages. In addition, most of the cases showed revitalization. Four cases received vestibular function tests, three of which had varying dysfunction of vestibular function, while the other one had normal vestibular function. Patients who had abnormal vestibular function showed much more severe hearing impairment. The three-generation family 1007193 had an autosomal recessive genetic characteristics, family 1007184 showed autosomal dominant inheritance of characteristics, family 1407278 were either autosomal dominant or X-linked dominant pattern. Through target genes capture high-throughput sequencing technology, we identified two candidate variants in the two members of family 1007184, named c. 2057G>A in EGFLAM and c. 1961C>T in ITGA8.

CONCLUSIONMeniere's disease has some genetic and familial aggregation in Chinese population, but its complex genetic pathogenic mechanisms need further study.

Adult ; Deafness ; Family Health ; Female ; Hearing Loss, Sensorineural ; etiology ; physiopathology ; Humans ; Inheritance Patterns ; Male ; Meniere Disease ; complications ; genetics ; physiopathology ; Middle Aged ; Migraine Disorders ; etiology ; Tinnitus ; etiology ; Vestibular Function Tests ; Vestibule, Labyrinth ; physiopathology