Contrary to the current concept of abortive regeneration of mammalian central axons, marked and functionally active regeneration of the mammalian CNS pathway has been found to occur. In addition, the concept seems to be now widely accepted that the axonal environment is non-permissive for regeneration because of inhibitory activity derived from oligodendrocytes and CNS myelin, and that therefore, those procedures that render the environment permissive for regeneration are essential, e.g., graft of peripheral nerves, Schwann cells or olfactory ensheathing cells, and application of antibody for neurite growth inhibitors with or without neurotrophic factor. However, this idea is not true. These procedures led to sparse, dispersed and largely aberrant regeneration. By contrast, in our experiment using a young rat, a very sharp cut of the pyramidal tract at the level of the medulla produced edema-free lesions without subse-quent formation of either cysts or scars, and eventuated marked regeneration, very close to normal in the amount, extension, path, formation of a compact bundle, and termination. This manner of marked regeneration was also observed in the cerebellifugal projection, auditory pathway, vestibulospinal tract, and dorsal column axons. Thus, we conclude that whether or not axonal regeneration occurs depends on local condition of lesion rather than the global CNS axonal environment. Even in adult animals, embryonic brain tissue grafts introduced into the lesion site, which presumably contain axonal guidance cues by excising homotopic embryonal structure, induce marked and functionally active regeneration. The graft contains comprehensive axonal guidance cues, although the detailed mechanism of axonal guidance have yet to be elucidated sufficiently. The best treatment for brain and spinal cord injury is obviously to reconstruct the damaged neural connections. The enormous potential for regrowth and self-organization arouse a great hope for therapeutic breakthoughs in the near future.
Hair cells are mechano-electrical transducers in the cochlea, vestibular organs, and the lateral line of fish. The mechanical stimulus displacing the hair cell hair bundle towards the taller stereocilia depolarizes the membrane. In this review article, the elementary natures of hair cell transducer functions, released neurotransmitters, and the efferent innervations are described.
The basic knowledge of molecular genetics is reviewed briefly, followed by a presentation of the results of an investigation of the vestibular schwannoma using molecular genetic techniques. The NF2 gene, responsible for neurofibromatosis type 2 (NF2), was mapped to the long arm of chromosome 22, and was isolated recently. NF2 is a hereditary disease characterized by bilateral vestibular schwannoma, but chromosome 22 allele loss and NF2 gene mutation are frequently observed not only in NF2 patients but also in non-familial unilateral vestibular schwannomas. In this inves-tigation, chromosome 22 LOH study and NF2 gene mutation analysis were performed in 94 tumor tissues consisting of 91 non-familial unilateral vestibular schwannomas, 2 vestibular schwannomas from NF2 patients, and 1 vagal schwannoma. LOH was stud-ied by using microsatellite markers located in the region of the NF2 gene on chromosome 22. Mutations were screened by SSCP for all 17 exons of the NF2 gene, and samples showing abnormal bands were sequenced by the conventional sequencing system to confirm the presence of mutation. LOH was detected in 35 cases (40%) among 87 cases in which LOH study was possible. Mutation analysis revealed 40 mutations in 36 of 94 tumors (38%). They were detected only in tumor DNA, and not in the constitutional DNA. Detected mutations were all predicted to result in either truncated or abnormal NF2 protein. LOH and/or mutations were detected in 52 cases (55%). These results conform to those of other similar studies, and are compatible with the two hit mutation model of Knudson. This suggests that the NF2 gene acts as a tumor suppressor gene and that its inactivation is an important step in the tumorigenesis of vestibular schwannoma.
The neurological and vestibular test for dysequilibrium is a time-consuming and troublesome task for most otolaryngologists in private out-patient clinics. Simplified neurological evaluation and vestibular tests were introduced for differential diagnosis of dysequilibrium. A stepping test involving ten steps with eyes open and closed, respectively, and evaluation of gaze nystagmus and positional nystagmus using an ultrared light camera are useful for the purpose. A simplified quantitative caloric test using 2 ml of ice water in necessary to detect the early stages of acoustic neurinome for unilateral cochlear symptoms or prolonged dysequilibrium. Using the merits of the patient's easy access to private out-patient clinics, a follow-up study revealed important findings in the central vestibular system, in which CT study had failed to find a lesion. Collaboration with neighboring hospitals and physicians with other specialities is essential for more accurate diagnosis and treatment of dysequilibrium.
One hundred ninety vertiginous patients were examined by several equilibrium examinations, magnetic resonance imaging, and MR-angiography (MRA). MRA findings were classified into five categories as follows: C-I) total vertebrobasilar system (VBS) stenosis; C-II) total unilateral vertebral artery (VA) stenosis; C-III) partial unilateral VA stenosis; C-IV) severe displacement of the basilar artery (BA); C-V) normal. The displacement angle of the BA was measured on the MR-angiogram. The mean angle was 152.2±39.7 degrees. In this study, those cases with an abnormal displacement angle less than 112.5 degrees were classified as C-IV. In central vestibular disorders (CVD), MRA abnormalities (C-I-IV) were detected in 60 out of 110 patients (54.5%), and abnormalities in the OKP and/or ETT were demonstrated in these patients. In the cases of CVD, the incidences of hyperlipidemia and hypotension were higher than that of anemia. A risk factors with aging, the incidence of MRA abnormalities was higher and the number of patients with orthostatic hypotension, increased.
Body balance can be examined by using a stabilometer. This device is very useful to record and estimate balance disorders. It was studied in this paper which factors of the stabilogram are the most reliable to show imbalance. 1. The patterns of the stabilogram are not stable. In the first and second examinations, the stabilogram showed different patterns. 2. The total length of the stabilogram showed disequilibrium quantitatively. The total length of the stabilogram became shorter by repeated examinations, and became longer by focusing their strengh on their feet, or body while examinations. 3. The center of the stabilogram showed the side of lesions by deviating to the lesion side. 4. Examination using a stabilometer is very useful for observing, treating, or estimating imbalance.
We evaluated the effects of rehabilitation in patients with vertigo using stabilometry. Kitasato method rehabilitation was perfomed 3 times a day for four weeks, in 31 patients. Twenty three other patients did not undergo this method. All patients had been taking difenidol hydrochloride (75 mg/day) for four weeks. Stabilometry was performed before and after rehabilitation in each patient (standing erect on both legs with eyes closed for 60 seconds). Total length and area were significantly decreased in the rehabilitation group. Those in the control group were not decreased. We concluded that rehabilitation was effective for treatment of vertigo. Total length and area of stabilometry were useful parameters for evaluation of rehabilitation in patients with vertigo.
Changes of Corneo-Retinal Potentials (CRP) were studied during routine equilibrium function tests and various visual conditions in healthy subjects. The changes in CRP were measured by amplitudes of horizontal 10° calibration. 1. In routine examinations, CRPs showed increased or decreased responses after each examination. 2. CRPs mostly increased after OKP tests during routine equilibrium function tests. However, in the examinations of OKN of 30°/sec, 60°/sec, and 90°/sec, CRPs showed similar increases for each OKN velocity. In the younger group (21-39 years), the CRPs were more increased than those in the older group (65- years) after OKP test. When OKP test was performed two times, there were no significant differences between the CRPs caused by the first examination and the second one. 3. CRPs showed a response decline after caloric test. 4. CRPs were examined every two minutes after electrodes were placed on the subjects, in an illuminated room with eyes open. The CRPs increased gradually until 8 minutes later. With eyes closed in an illuminated room, and with eyes open and closed in a dark room, CRPs decreased until 8 minutes later. 5. CRPs during equilibrium function tests were changed by visual conditions (light or dark). However they were not changed by eye movements.
To estimate the turning sensation caused by Coriolis stimulus (cross-coupled rotation), motion of the endolymph in the semicircular canals during the stimulus was deduced by an approach of mechanics, and sensory output from the semicircular canals was estimated. Coordinate systems fixed in space, a horizontally rotating device, subject's head, and 6 individual semicircular canals were defined so that canal motion and turning sensation during Coriolis stimulus were simply presented. Transformations between the coordinate systems were given in matrices. A simple model of the semicircular canal was hypothesized, and an equation of motion of the endolymph in the semicircular canal-fixed coordinate system was formulated. By solving the equation, rotating angle of the endolymph was estimated. Proportional relation between turning sensation and the rotating angle of the endolymph was further hypothesized. It was then shown that the turning sensation derived from each semicircular canal is equivalent to a half of the angular velocity change around an axis perpendicular to the individual canal plane if every semicircular canal contributes equally to the turning sensation in a three-dimensional space. In the following paper, turning sensations derived by the whole semicircular canal system during a single Coriolis stimulus and cyclic Coriolis stimuli are discussed.
This study investigated age-related changes of how visual information affects control of body sway in community-dwelling older adults. The subjects were 637 older adults (263 males, 374 females) aged 67 to 91 years living in Nangai Village in Japan. The subjects, with shoes on, stood stationary and upright on a force platform with their feet together (Romberg stance) for 20 seconds with eyes open and eyes closed, respectively. Body sway length and body sway area were calculated as magnitude of body sway. The four parameters used to examine the effect of visual information on postural control were calculated. They were body sway length difference, body sway area difference, body sway length ratio, and body sway area ratio. The body sway length ratio and the body sway area ratio did not change with advancing age. The body sway length difference and body sway area difference changed with age. They increased with age from age 67 to 79, and then they decreased beyond 80 years of age. Measurements of all of the four parameters in the male subjects were significantly higher than those in the female subjects.
In order to clarify whether the galvanic body sway test (GBST) is useful for differential diagnosis of lesions in patients with absent vestibular evoked myogenic potentials (VEMP), clinical records of patients with absent GBST were reviewed. Patients were 4 men and 10 women. Their ages ranged from 32 to 81. Diagnoses were vestibular neuritis in 6 patients, acoustic neuroma in 7 patients, and temporal bone fracture in one patient. GBST were performed using a stabilometer. As stimulation, 0.6 mA electrical stimuli were presented for 3 seconds. Electrodes were placed on the mastoid and the forehead. For recording VEMPs, electrodes were placed on the upper half of the sternocleidomastoid muscle and the lateral end of the upper sternum. As stimulation, 95 dBnHL clicks were presented at the rate of 5 Hz. Signals were amplified and bandpass-filtered (20-2000 Hz). One hundred responses were averaged. Whereas all of the 14 patients showed abnormal caloric responses, 4 patients (29%) showed normal VEMPs. These results suggested that GBST is not always useful for differential diag-nosis of retro-labyrinthine lesions from labyrinthine lesions in patients with abnormal VEMPs, while GBST could be useful for differential diagnosis in patients with abnormal caloric responses. We should establish other clinical testing for differential diagnosis of retro-labyrinthine lesions from labyrinthine lesions in patients with abnormal VEMPs.
A 53-year-old woman with cerebellar infaction who complained of dizziness as an isolated symptom was presented. She had a normal brain CT scan and no neurological abnormalities at the onset, and she was initially diagnosed as having peripheral vestibular disorder. However, her oculomotor findings obtained 1 week after the onset revealed an impaired pursuit eye movement, lower gain on optokinetic nystagmus, and a failure of visual suppression on a caloric nystagmus test. From the neurootological findings, we suspected that she had a cerebellar lesion and an MRI revealed increased signal intensity in the cerebellar hemisphere. Consequently, the patient was diagnosed as having cerebellar infarction. Symptoms of cerebellar infarcts are frequently similar to those of peripheral vestibular disease, and such patients may be overlooked if neurootological tests are not performed. In particular, oculomotor tests in patients with vertigo/dizziness are very useful to differentiate central nervous system disorders from peripheral vestibular disorders.
Purpose: To determine the functional brain localization of the eye tracking test (ETT), we studied healthy volunteers by functional magnetic resonance imaging (fMRI). Methods and Materials: Three healthy volunteers underwent examinations using our 1.5 Tesla Magnetic Resonance Imager (Signa 1.5) under one shot echoplanar imaging (EPI) sequence (TR 4000 msec, TE 60 msec, FOV 24 cm, 8 mm thickness, 64 X 64 matrices, and horizontal slices). These images were analyzed by T test using "STIMULATE". The results were superimposed on three-dimensional brain surface images of themselves. The task was saccadic and smooth pursuit. The ETT target was projected from the operating room to a translucent screen in the scanning room. Results and Discussion: The frontal eye field, the associative visual cortex, and the lateral occipito-temporal cortex were well detected. In our study, the frontal eye field included Brodmann areas 4 and 6, but not 8. In all cases, saccadic and smooth pursuit showed similar activated patterns. However, the latter showed higher statistical confidence. Cerebellar activation was also detected, but the interslice gaps may have be too wide to detect the localization. Half coronal gapless thin slices should be employed for cerebellar analysis. Conclusion: FMRI is a very powerful method to analyze the brain localization of the ETT.