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Cochlear implantation is now an established technology for restoring hearing in profoundly deaf patients. Adults who have lost all useful hearing in both ears are suitable for cochlear implantation if they are profoundly deaf (generally this implies hearing thresholds of 100 dB nHL or worse, across the frequency range 125 to 8000 Hz), with aided hearing thresholds worse than 60 dBA for the frequencies 250 to 4000 Hz and scoring less than 30% in a test of sentence discrimination, using their hearing aids and without lip reading. We describe a patient with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) who became profoundly deaf and who has successfully undergone cochlear implantation and rehabilitation.
A right handed secretary with MELAS syndrome, and a confirmed A to G mutation at nucleotide 3243 in the mitochondrial genome, was referred to the cochlear implant programme of The Royal National Throat, Nose, and Ear Hospital. She had insulin dependent diabetes, congenital cataracts, short stature, leg weakness, fatigue, and hearing loss. She had never had encephalopathy or strokes. Her mother is also diabetic, has glaucoma, and has a lesser degree of deafness, and her sister has been profoundly deaf from adolescence in addition to having severe mental retardation. The patient had begun to experience bilateral hearing loss at the age of 22, with slow deterioration up to the age of 29, by which time she was profoundly deaf in the right ear. By the age of 30 she was also profoundly deaf in the left ear and had developed tinnitus. She had no spontaneous vertigo, but sudden movements could leave her temporarily unsteady. At the age of 31 she was referred for assessment for cochlear implantation. Her ability to communicate with her family was severely restricted because of her deafness. She had developed a modest lip reading ability and was able to lip read her husband to a limited extent, but relied greatly on finger spelling and written information. Her own voice quality had begun to deteriorate. She was found to have no measurable hearing thresholds except for a 250 Hz tone at 105 dB nHL in the right ear. No tests of speech discrimination were possible, as she had virtually no hearing in either ear. Middle ear impedence was normal, and she had normal bilateral vestibular function on caloric testing. Auditory brain stem responses and electrocochleography showed no peaks in response to wide band clicks presented to either ear at 100 dB nHL, consistent with profound sensorineural deafness. Electrical stimulation of the cochlea, using sinusoidal stimuli presented through a transtympanic needle electrode placed through the tympanic membrane onto the promontory of the middle ear,1 2 gave rise to a subjective sensation of hearing in both ears, with better performance on gap detection and temporal difference limen tests on the right. A CT scan of the temporal bones was normal.
The findings listed above showed her to be within the criteria for cochlear implantation, and she was implanted in the right ear at the age of 32 with a Nucleus 22 multichannel implant. All 22 electrodes were inserted into the cochlea and there were no surgical complications.
Subsequent switch on and rehabilitation went well, and the patient has made good progress. She is able to discriminate environmental sounds well, including different birdsongs, and participate in conversation. Verbal communication with her family has improved. There have been no specific problems with the implant and she is able to converse on the telephone using the implant. The patient has resumed full time work in an office. The tinnitus has remained stable, and there have been no vestibular problems. At the 2 year assessment she scored 97% correct on CUNY/UCL sentences (a British adaptation of a sentence discrimination test developed at City University, New York), using her implant and lip reading and 92% correct on BKB (Bamford, Kowal and Bench) sentences (another speech discrimination test) using her implant but without lip reading. Speech production was within normal limits, although the narrow pitch range reflected her slightly flat pattern of intonation.
MELAS syndrome was first described in 1984 and is one of a group of mitochondrial cytopathies, associated with point genetic mutations. In the brain the characteristic abnormalities are basal ganglia calcification and focal lesions of cerebellar and cerebral atrophy, resulting from cellular rather than vascular dysfunction.3Although it does not feature in the acronym, hearing loss is a common finding in MELAS. Reports of large kindreds and patient series have shown that at least 50% of patients have a moderate or severe sensorineural hearing loss: 21 of 28 patients with MELAS in an Australian series were deaf,4 as were eight of 14 patients in a British series.5 The phenotypic expression of the mutation is subject to at least three constraints; the percentage of mutant mitochondrial DNA in the target tissue (which has at most a loose correlation with clinical lesions),5 the oxidative stress to which different organs or cell populations are exposed, and as yet unidentified collaborating somatic mutations which enhance selective aspects of the syndrome.
The cochlea is an organ exquisitely vulnerable to oxidative stress. The outer hair cells have a precarious, indirect metabolic support from Deiter cells, and the stria vascularis is both metabolically very active and non-mitotic, hence further subject to mutation accumulation. Recently detailed audiological findings have been reported in 18 patients with MELAS, and the authors argued that the hearing loss in their patients was entirely due to cochlear lesions.4There were excellent speech discrimination scores in six of 12 patients with mild to moderate deafness, and excluding severe and profoundly deaf patients with absent responses, there were normal and symmetric brain stem evoked responses in 18 of 20 latencies recorded from 10 patients. Promontory stimulation testing in two patients was normal, and CT and MRI were reported as showing no lesions which could contribute to hearing loss.
Central auditory lesions have been reported as a cause of hearing loss in MELAS. Imaging studies using both CT and MRI have shown that the occipital and parietal lobes and cerebellum are the brain regions most likely to show focal lesions,3 and a perfusion study using123I-IMP SPECT, and acetazolamide challenge, showed that patients with MELAS typically have hypoperfusion of the occipital and parietal lobes, with a significant defect in perfusion reserve.6 A case report of a patient who died after having had severe seizures and stroke-like events, and who had had multiple imaging studies, showed mild temporal lobe atrophy at necropsy with associated spongy degeneration of the cortex.7 All cortical regions were demonstrated radiologically and pathologically to be abnormal in this patient, with the occipital lobe showing the most marked hypoperfusion. She had become deaf 2 years before her marked clinical deterioration.
The patient we report has had no seizures or stroke-like episodes. Her presenting complaint was hearing loss, which progressed over 8 years to profound deafness. Her selection as a candidate for cochlear implantation was straightforward, and she has been successful in adapting to the device and has gained a significant benefit from it. The performance of the patient in the BKB word tests places her in the top 5% of adult performers in our patient series. Another patient with profound deafness and MELAS, who had had seizures and strokes, has recently been reported incidentally in a large series to have been implanted with a successful outcome, but unfortunately details were not provided.4
The fact that this patient has gained considerable benefit from her cochlear implant raises the possibility that other patients with MELAS syndrome and profound sensorineural deafness could benefit from this procedure.