Cochlin-tomoprotein: a novel perilymph-specific protein and a potential marker for the diagnosis of perilymphatic fistula.

BACKGROUND: Perilymphatic fistula (PLF) is an abnormal connection between the inner and middle ear. A procedure for obtaining definite proof of a PLF remains elusive, and methods of diagnosis remain controversial. To date, there is no clinically relevant biochemical marker for perilymph leakage. Using proteomic analysis of inner ear proteins, we have previously found unique properties of cochlin, encoded by the COCH gene. We detected 3 cochlin isoforms (p63s, p44s and p40s) in the inner ear tissue and a short 16-kDa isoform of cochlin-tomoprotein (CTP) in the perilymph. Since cochlin was found to be highly specific to the inner ear, we speculated that CTP might also be specific to the perilymph. The aim of this study was to determine whether CTP, a novel perilymph-specific protein, could be used as a marker for the diagnosis of PLF. METHODS: By Western blotting, we investigated the specificity of CTP expression in a range of body fluids that included perilymph, serum, saliva and cerebrospinal fluid. To elucidate the detection limit of CTP, serially diluted recombinant human (rh)CTP as well as human perilymph was tested. RESULTS: CTP was selectively expressed in all 20 perilymph samples tested, but not in 77 samples of the other body fluids. The detection limit of rhCTP was 0.27 ng or 0.022 microl of perilymph per well on Western blot analysis. CONCLUSION: The results strongly suggest that CTP can be a specific marker of perilymph leakage. Moreover, CTP has the potential to be a biochemical marker that allows a definitive diagnosis of the etiology of PLF-related hearing loss and vestibular disorders.

Pathological localization of so-called posterior canal BPPV.

OBJECTIVE: Based on the hypothesis that the origin of nystagmus is from the posterior canal (PC), the nystagmus in the head hanging and sitting position should be mirror images. To clarify the anatomical origin of positioning nystagmus in BPPV patients, we analyzed the positioning nystagmus of benign paroxysmal positioning vertigo (BPPV) patients three-dimensionally. METHODS: Twenty-six patients with BPPV participated in this study. The positioning nystagmus was recorded in complete darkness from the patient's left eye by means of an infrared CCD camera. We performed three-dimensional analysis of nystagmus using video image analysis system (VIAS). Subsequently, the rotation axis of the 3D eye movements of the positioning nystagmus was calculated. RESULTS: Among the 26 patients tested, 20 patients demonstrated the axes of nystagmus in good or relatively good alignment to the PC axis. However, in 11 of these 20 patients there was poor alignment of the axis of nystagmus in the sitting position to the PC axis. In addition, six patients showed axes of nystagmus with poor alignment to the PC in the head hanging position. Among them, two patients exhibited axes of nystagmus in good alignment with the anterior canal, in spite of diagnosis of these patients as PC BPPV by experienced examiner based on the positioning nystagmus test. CONCLUSION: These results demonstrated that only one-third of patients who were diagnosed as BPPV, could be diagnosed as true BPPV which originates from a PC pathology. Besides the possibility that the pathology may originate from the AC, it is still unclear which part of the inner ear may be the candidate site of origin of the pathology of BPPV in the other 15 patients.

Three-dimensional analysis of eye movements using four times high-speed video camera.

In order to record and analyze the rapid eye movement non-invasively in human subjects, a four times high-speed video camera (4TC) with a new computer software was developed and utilized. Nine healthy volunteers and four patients with vestibular dysfunction participated in this study. Caloric stimulation was applied to the healthy subjects and the eye movements were recorded using a standard camera (SC) and a 4TC. In four patients, the positional and/or positioning nystagmus was recorded using SC and 4TC. Analysis of the eye speed of the quick phase of nystagmus was performed manually from the print out of the chart. The quick phase of the caloric nystagmus was adequately analyzed from the data using 4TC. However, using SC the sampling rate was not sufficiently enough for this purpose, as prospected. The adaptability of the 4TC in clinical examination is exactly similar to that of SC, because of the size and weight of the camera. Although the time taken to analyze eye movements using 4TC is about four times longer than that using SC, this system is quite useful and adequate for analyzing the quick eye movements in vestibular nystagmus, in an out-patient clinic set up.

A head-mounted visual stimulator for neurotological examination.

OBJECTIVES: Presently, the neurotological tests, using visual stimulation, such as optokinetic nystagmus test (OKN), eye-tracking test (ETT) is being widely used for the diagnosis of vertigo or disequilibrium. The problems of these tests are the large size of the visual stimulator and therefore a wide space requirement. Even if a small apparatus is developed, the apparatus itself would be very expensive. In this study, we developed a small visual stimulation test system comprising the virtual visor, which receives an image for visual stimulation from an on-line computer. METHODS: Using smooth pursuit and optokinetic stimulation onto a virtual visor we assessed the ENG recording in 20 normal subjects. RESULT: We found the 30 degrees /s OKN, horizontal eye tracking were adequately stimulated by this technique with reliable results. CONCLUSION: This new method of smooth pursuit and optokinetic stimulating by a virtual visor is capable of producing reliable results and may be used in the clinical laboratory of vertigo. However, this stimulator also has some limitations, mainly because of the visual angle of the virtual visor stimulator.

A comparative study on the observation of spontaneous nystagmus with Frenzel glasses and an infrared CCD camera.

OBJECTIVES: To compare the usefulness of a CCD camera with infrared illumination (IR-CCD camera) over Frenzel glasses (F Glasses) for the observation of spontaneous nystagmus, the incidence and direction of nystagmus, and the frequency, amplitude and slow phase of spontaneous nystagmus. METHODS: One hundred vertiginous patients, fifty-three females and forty-seven males participated in this study. Before undergoing routine neurotological examination, their eye movements were recorded by electronystagmogram (ENG) in conjunction with observations of eye movements under F glasses and through an IR-CCD camera. The data was collected from patients who exhibited spontaneous nystagmus either under F glasses or the IR-CCD camera. RESULTS: Thirty-three patients showed spontaneous nystagmus under F glasses. On the other hand, under the IR-CCD camera, all patients examined exhibited spontaneous nystagmus. The frequency of nystagmus was not significantly different between these two systems. However, the amplitude and slow phase velocity exhibited significantly larger values under the IR-CCD camera in patients with spontaneous nystagmus both under the IR-CCD camera and F glasses. CONCLUSION: From these observations and evidence, the IR-CCD camera can be recommended as a more useful system and powerful tool for neurotological examination than F glasses.

Rotation vectors of slow and quick phase of caloric nystagmus.

OBJECTIVE: The purpose of this study was to elucidate the rotation axes of the slow and quick phase of the caloric nystagmus using the video-oculographic technique. METHODS: Subjects were placed in a supine position and cold-water stimulation was applied to the right ear canal. The eye movements were recorded in complete darkness by a high-speed infrared CCD camera. The sampling time of the camera was 132Hz with 640×480 effective pixels. RESULTS: The rotation vectors were calculated from the printed-out chart of the 3D analysis data of the caloric nystagmus. The directions of the rotation vector of the quick phase of the nystagmus were almost opposite to those of the slow phase. The average planer equations of the slow and quick phase of the nystagmus in all subjects were 0.399x+0.1477y-0.8656z=0 and -0.3970x-0.1940y+0.8559z=0, respectively. CONCLUSION: We demonstrated that the slow phase and quick phase of the vestibular nystagmus are along with the same axes in human subjects.

Cochlin-tomoprotein (CTP) detection test identifies traumatic perilymphatic fistula due to penetrating middle ear injury.

CONCLUSIONS: The cochlin-tomoprotein (CTP) detection test can be used to make a definite, objective diagnosis of traumatic perilymphatic fistula (PLF), and therefore offers valuable information on patient selection for surgical treatment. OBJECTIVES: Penetrating middle ear injury can cause traumatic PLF, which is a surgically treatable otologic emergency. Recently, we have reported on CTP, a novel perilymph-specific protein. The purpose of this study was to determine if the CTP detection test is useful for the diagnosis of traumatic PLF. METHODS: This was a prospective study of CTP detection in penetrating middle ear injury cases with tympanic membrane perforation and hearing loss. RESULTS: A total of seven individuals were included in this study. CTP was detected in three of four cases with posterosuperior quadrant perforation of the tympanic membrane. In one of these three cases, even though the high resolution CT scan was not suggestive of PLF and the perilymph leakage could not be visualized intraoperatively, the CTP detection test was able to detect PLF. In two cases, the preoperative positive test results enabled us to make a diagnosis of PLF and a decision for surgical treatment. CTP was not detected in the cases with anterior or inferior tympanic membrane perforation.

3D analysis of spontaneous nystagmus in early stage of vestibular neuritis.

OBJECTIVE: The pathological localization of vestibular neuritis is still controversial. Analyses of the spontaneous nystagmus support the temporal bone studies, which indicated the location of the pathology to be in the superior vestibular nerve. However, based on the data from the head impulse testing the pathology is in the vestibular nerve including the inferior branch. METHODS: Twenty-three patients with vestibular neuritis participated in this study. The spontaneous nystagmus was recorded within 1 week after the onset of the disease. Three-dimensional analysis of the nystagmus was performed using video image analysis system. The rotation axis was calculated and compared to the anatomical axes of the semicircular canals. RESULTS: The axes of the spontaneous nystagmus in all patients were scattered around the axes of horizontal and anterior canals, especially between the compound axis of anterior and horizontal canals and the axis of horizontal canal. The statistical analysis revealed that in the quite early stage of the disease (day 0-2 of the attack), the spontaneous nystagmus tended to have more torsional eye movements as compared to the less early stage (day 3-6). CONCLUSION: The present study strongly suggests that the pathology of vestibular neuritis is in the superior vestibular nerve branch. Also it can be speculated that at the early stage of this disease, the pathology is in the whole branch of the nerve. Subsequently, the anterior canal branch recovers faster than the horizontal canal branch.

3D analysis of cough-induced nystagmus in a patient with superior semicircular canal dehiscence.

We report here about a case (female patient) with superior semicircular canal dehiscence (SSCD). This patient presented with pressure-induced rotatory vertigo when she coughed or strained at stool. Loud sounds or Valsalva maneuver did not evoke any sensation of vertigo and/or disequilibrium. By contrast, when she coughed, vertical-rotatory nystagmus was clearly induced. The 3D analysis of cough-induced nystagmus revealed that the rotation axes of the nystagmus were well aligned with the right superior semicircular canal. In conjunction with the temporal bone CT study, the pathological localization in the inner ear in this patient was confirmed to be in the right superior semicircular canal.