Analysis On The Effectiveness Of Cochlear Implantation In Patients With Auditory Neuropathy Spectrum Disorder And Its Correlation With Gene

Auditory neuropathy spectrum disorder (ANSD)is also known as auditory neuropathy, and it is audiologically characterized by absent or abnormal auditory brainstem evoked responses (ABR) but normal OAE, as well as normal or elevated pure tone hearing threshold to different degree but significantly impaired speech comprehension which is disproportionable to the degree of hearing loss. It is believed that ANSD is retrocochlear disease, which is used to describe auditory disorder due to dysfunction of the synapse of the inner hair cells, and/or the auditory nerve itself.Due to its uncertainty of lesion sites, there is still no definitely accepted treatment. Cochlear implantation(CI) was used to treat ANSD in the past, which was confirmed to be effective in some cases while not in others. It was deduced that the efficacy may be related to the different pathological changes. ANSD can have different pathological changes, and will show different clinical symptoms, which of course also has different pathophysiological mechanisms. In 2008, Starr and his colleagues adviced classifying the term auditory neuropathy into different types according to the sites of this disorder. If the lesion of ANSD was located at the auditory nerve while the inner hair cells and synapses were normal, the type of the disorder should be defined as "auditory nerve disorder". If the inner hair cell synapses were abnormal but the auditory nerve was normal, the type of the disorder should be defined as "auditory synaptic disorder". The classification of the lesion was significant to provide guidance for clinical intervention such as CI. Recently, with the rapid development of molecular biology, the pathological mechanism was found at the molecular level, indicating that the lesion sites can be determined according to different gene mutations, especially for non-syndromic auditory neuropathy (NSAN). In order to explore the effectiveness of CI in patients with ANSD. genetic tools were used for guidance.The patients with ANSD who accepted Cl in 2008-2015 year were collected, and the efficacy of CI was assessed. Furthermore, ANSD related genetic screening was performed in 13 cases to analyze the effectiveness of CI in patients with ANSD which had different gene mutations.The thesis covers two parts:PART1:The Intervention and Effectiveness of Cochlear Implantation in Patients with Auditory Neuropathy Spectrum DisorderThe tests of pure-tone audiometry, Speech Intelligibility Rating (SIR), Categories of Auditory Performance (CAP) and Meaningful Auditory Integration Scale (MAIS) were performed in 19 prelingually deafened patients with ANSD which had severe or profound hearing impairment and 4 post-lingually deafened patients with ANSD which had severe or profound hearing impairment after CI. The outcomes were compared between patients with ANSD and those with non-syndromic congenital deafness.The average aided hearing threshold of 12 ANSD patients after CI was 38.75±6.08 dB. There was no significant difference in scores of vocalization behavior and spontaneous alerting to sound between ANSD and non-syndromic prelingually deafened patients after CI (P>0.05). There was significant difference in scores of speech comprehension and MAIS between ANSD and non-syndromic prelingually deafened patients after CI (P>0.05). The scores of speech comprehension and MAIS of ANSD prelingually deafened patients after CI were significantly lower than those of non-syndromic prelingually deafened patients after CI. There was no significant difference in scores of CAP and SIR between ANSD and non-syndromic post-lingually deafened patients after CI(P>0.05).The ANSD prelingually deafened patients with severe or profound hearing impairment and non-syndromic hearing-impaired patients showed no significant difference in the ability of vocalization behavior and spontaneous alerting to sound. The ability of speech comprehension of ANSD prelingually deafened patients after CI was significantly lower than that of non-syndromic prelingually deafened patients after CI. There was no significant difference in auditory and speech ability between ANSD and non-syndromic post-lingually deafened patients after CI..PART2:The Effectiveness of Cochlear Implantation in Patients with Auditory Neuropathy Spectrum Disorder and Its Correlation with GeneThere were 11 patients with ANSD which accepted CI in Department of Otolaryngology Head and Neck Surgery of Chinese PLA General Hospital between October,2009 and March,2014, and 2 patients with ANSD which underwent CI in that of Hainan Branch of Chinese PLA General Hospital between February,2012 and August,2014,13 cases in total. The peripheral venous blood was collected and the genomic DNA was extracted. Target area capture+high-throughput sequencing technology was used to screen the mutations of PJVK gene, OTOF gene, DIAPH3 gene and other ANSD related genes. Because of the discovered possible pathogenic mutations, the effectiveness of CI in patients with different ANSD related gene mutations can be analyzed from the perspectives of postoperative speech rehabilitation.We detected 10 possible pathogenic gene mutations of the OTOF gene in exon region of 5 patients in this study. The other patients did not have the OTOF gene mutations. There were no mutations of PJVK gene, AIFM1 gene, DIAPH3 gene and other ANSD related genes in this study. Among the 5 patients, OTOF gene mutation at p.E 793 x and c.765+1g> c was detected in 1 patient; OTOF gene mutation at p.N727 s was detected in 1 patient; OTOF gene compound heterozygous mutation at p.Y 1133 x and c.5833 delg was detected in 1 patient; OTOF gene compound heterozygous mutation at pG558A fsX21, p.Q 994 v fsX6 and p.Q 265L was detected in 1 patient; compound heterozygous mutation at p.G 541 s and 795 s fsX5 p.L was detected in 1 patient. There was no significant difference in scores of MAIS between 5 prelingually deafened patients with ANSD who carried the OTOF gene mutation and non-syndromic deafened patients after CI (P>0.05). There was no significant difference in scores of MAIS between 7 prelingually deafened patients with ANSD who did not carry the OTOF gene mutation and non-syndromic deafened patients after CI (P>0.05).There were 10 possible pathogenic mutations in this study, which were all found in Chinese population. It was indicated that the OTOF gene was associated with the occurrence of ANSD in Chinese population. There was no significant difference in auditory and speech ability between 5 prelingually deafened patients with ANSD who carried the OTOF gene mutations and non-syndromic deafened patients after CI.There was no significant difference in auditory and speech ability between 7 prelingually deafened patients with ANSD who did not carry the OTOF gene mutations and non-syndromic deafened patients after CI.