Gail Ishiyama

The relevance of migraine in patients with Ménière's disease

Conclusion. Coexistent migraine affects relevant clinical features of patients with Ménières disease (MD). Objective. Epidemiological studies have shown an association between migraine and MD. We sought to determine whether the coexistence of migraine affects any clinical features in patients with MD. Patients and methods. In this retrospective case-control study of University Neurotology Clinic patients, 50 patients meeting 1995 AAO-HNS criteria for definite MD were compared to 18 patients meeting the same criteria in addition to the 2004 IHS criteria for migraine (MMD). All had typical low frequency sensorineural hearing loss and episodes of rotational vertigo. Outcome measures included: sex, age of onset of episodic vertigo or fluctuating hearing loss, laterality of hearing loss, aural symptoms, caloric responses, severity of hearing loss, and family history of migraine, episodic vertigo or hearing loss. Results. Age of onset of episodic vertigo or fluctuating hearing loss was significantly lower in patients with MMD (mean±1.96*SE=37.2±6.3 years) than in those with MD (mean±1.96*SE=49.3±4.4 years). Concurrent bilateral aural symptoms and hearing loss were seen in 56% of MMD and 4% of MD patients. A family history of episodic vertigo was seen in 39% of MMD and 2% of MD patients.

A longitudinal study of oculomotor function in normal older people

Cross-sectional studies have found declines in most measures of oculomotor function in older subjects compared to young controls, but no prior study has followed the same subjects over time. We measured saccade peak velocity, saccade delay time, smooth pursuit, optokinetic nystagmus (OKN), visual-vestibular-ocular-reflex (VVOR), fixation suppression of the vestibulo-ocular reflex (VOR-fix), and the vestibulo-ocular reflex in 53 subjects (older than 75 years) able to complete at least 9 yearly evaluations. In addition at each visit all patients underwent a complete history and examination, a gait and balance assessment, mini-mental status evaluation, and visual acuity testing. A subset of subjects completed 12 yearly evaluations (14 patients). Despite significant declines of most variables over time, smooth pursuit gain and saccade peak velocity remained stable during the duration of the study both in the 9-year group and the patients completing 12 years. Decline in OKN, VVOR, and VOR were significantly correlated (P<0.001) with decline in the Tinetti gait and balance score, even after controlling for age. In normal healthy older subjects, smooth pursuit and saccade peak velocity are relatively maintained while OKN, VVOR, and VOR function decline. The significant correlation between decline in oculomotor measures and gait and balance measures (even after controlling for age) suggests a common mechanism for the decline in both measures.

Clinical features and associated syndromes of mal de debarquement

ObjectiveTo investigatethe clinical features and naturalhistory of mal de debarquement(MdD).DesignRetrospective casereview with follow-up questionnaireand telephone interviews.SetingUniversity Neurotology Clinic.PatientsPatients seen between1980 and 2006 who developed apersistent sensation of rocking orswaying for at least 3 days after exposureto passive motion.Main outcome measureClinical features,diagnostic testing, and questionnaireresponses.ResultsOf 64 patients(75 % women) identifiedwith MdD, 34 completed follow-upquestionnaires and interviews in2006. Most patients had normalneurological exams, ENGs andbrain MRIs. The average age of thefirst MdD episode was 39 ± 13years. A total of 206 episodes wereexperienced by 64 patients. Ofthese, 104 episodes (51 %) lasted> 1 month; 18 %, > 1 year; 15 %, > 2years; 12 %, > 4 years, and 11 %, > 5years. Eighteen patients (28 %) subsequentlydeveloped spontaneousepisodes of MdD-like symptomsafter the initial MdD episode.There was a much higher rate ofmigraine in patients who went onto develop spontaneous episodes(73 %) than in those who did not(22 %). Subsequent episodes werelonger than earlier ones in mostpatients who had multiple episodes.Re-exposure to passivemotion temporarily decreasedsymptoms in most patients (66 %).Subjective intolerance to visualmotion increased (10 % to 66 %)but self-motion sensitivity did not(37 % to 50 %) with onset of MdD.ConclusionThe majority of MdDepisodes lasting longer than 3 daysresolve in less than one year but theprobability of resolution declineseach year. Many patients experiencemultiple MdD episodes. Somepatients develop spontaneousepisodes after the initial motiontriggeredepisode with migrainebeing a risk factor.

Imbalance and vertigo: the aging human vestibular periphery.

Dizziness, vertigo, and imbalance are likely the most common presenting complaints among patients 75 years and older in office practices. Although the cause of falls among the aging population is multifactorial, several studies have implicated senescence of the vestibular periphery. It is imperative that clinicians correctly diagnose and treat dizziness and vertigo in the geriatric population, as vestibular impairment is quite responsive to specifically designed rehabilitation. One of the most common causes of vertigo in older adults is benign positional vertigo. The aging otolithic membrane, alterations in calcium metabolism, and microvascular ischemia may all play a role. An age-related deterioration of vestibular function on quantitative testing has been documented, and the age of onset correlates with the age-related cellular loss in the vestibular periphery. Furthermore, longitudinal tests of decline in vestibular function correlate with decline in gait and balance on testing. It is likely that senescence of both the central and peripheral vestibular pathways plays a role in age-related decline in balance. Vestibular disorders in the older patient are associated with a diminished level of independent activities, an increased incidence of falls, and possibly also clinical depression. The authors laboratory is delineating the immunohistochemical expression of proteins in the basement membrane of the vestibular system in older adults as a potential cause of the age-related decline in sensory cell and neuronal number.

Regional estimates of hair cells and supporting cells in the human crista ampullaris

Regional estimates of type I and type II vestibular hair cells (HC) and supporting cell (SC) numbers were obtained from the horizontal crista ampullaris by using design‐based stereology in human. Cristae were microdissected from temporal bones obtained post‐mortem (N = 16, age range 26–98 years). Three groups were made according to age: group 1, n = 5, ages between 26 and 67 years, average age 51 years; group 2, n = 4, average age 84 years; and group 3, n = 7, average age 94 years. For group 1, the average total HC number was 8,005 ± 214, corresponding to 4,119 ± 107 type I HC, 3,886 ± 117 type II HC, and 10,274 ± 224 SC. The type I:type II HC ratio was 1.06 ± 0.01, and HC density was 0.80 cells/100 μm2. For group 2, the average total HC number was 7,074 ± 489, corresponding to 3,733 ± 212 type I HC, 3,341 ± 314 type II HC, and 9,321 ± 858 SC. The type I:II HC ratio was 1.12 ± 0.06, and HC density was 0.75 cells/100 μm2. For group 3, the average HC number was 6,009 ± 327, corresponding to 3,380 ± 223 type I HC, 2,628 ± 235 type II HC, and 10,185 ± 182 SC. The type I:II HC ratio was 1.34 ± 0.10, and HC density was 0.63 cells/100 μm2. A significant decline in type I, type II, and total HC number and density was found in groups 2 and 3, with individuals exceeding the average human life span.

Drop attacks in older patients secondary to an otologic cause

Article abstract— The clinical features and treatment of seven patients with drop attacks attributable to inner ear disease presenting after age 65 are described. A neurologic or cardiovascular cause of drop attacks was initially suspected. Audiovestibular testing documented a unilateral inner ear disorder. The salient clinical features of these cases are discussed. The patients underwent ablative vestibular surgery, and all compensated well and were free of vertigo and falls up to 10 years postoperatively.

Gentamicin ototoxicity: clinical features and the effect on the human vestibulo-ocular reflex

Conclusions. Gentamicin ototoxicity presents with gait imbalance and oscillopsia, but only rarely with hearing loss and vertigo. Sinusoidal rotational stimuli with high accelerations such as the bedside head-thrust test or rotational step changes in velocity are useful to diagnose bilateral vestibulopathy. Objective. To describe the salient clinical features and vestibular testing results in gentamicin ototoxicity. Patients and methods. A retrospective review of the quantitative vestibular function testing results for patients presenting to the UCLA Neurotology Clinic with gentamicin ototoxicity over the past 10 years (n=35). Results. All patients presented with imbalance and 33 out of 35 had oscillopsia. Three patients reported a noticeable change in hearing and five reported vertigo. Of the 35 patients, 15 were in renal failure at the time of gentamicin administration. Patients with pre-existing peripheral neuropathy compensated poorly. Sinusoidal rotational testing demonstrated profoundly decreased gain and increased phase lead over the entire frequency range, with a subset of patients having relatively preserved gain at the intermediate frequencies (0.8–1.6 Hz) and low acceleration (<30°/s). There was little or no response to high acceleration step changes in velocity. The time constant measured both by sinusoidal and step responses was ultra-low. All patients tested had a positive head-thrust test bilaterally.

Estimation of the number of nerve fibers in the human vestibular endorgans using unbiased stereology and immunohistochemistry

The objective of this study was to obtain estimates of the number of nerve fibers in the human crista ampullaris and utricular macula from normal individuals using unbiased stereology and immunohistochemistry. Vestibular endorgans with the attached vestibular nerve stump were microdissected from the temporal bones. Specimens were divided into two groups. The first group (group 1, N = 8, age range, 68-98 years old, mean = 87 years) was fixed with paraformaldehyde and post-fixed with osmium tetroxide. The second group (group 2, N = 5, age range, 80-98 years old, mean = 86.6 years) was fixed with paraformaldehyde, immunoreacted with monoclonal antibodies against neurofilaments, and post-fixed with osmium tetroxide. The endorgans of both groups were embedded in resin and 2-mum thick sections were made. Estimates of the number of nerve fibers were obtained using an unbiased stereological method, the fractionator. The diameter distribution of nerve fibers was also obtained. The average number of fibers in the horizontal, posterior and superior cristae of individuals in group 1 (N = 14 cristae) was 1424+/-320 (CV = 0.22). The average percentage of small (less than 3 microm), medium (between 3 and 5 microm) and large (more than 5 microm) size fibers was 22.4%, 51.5% and 26.1%, respectively. In group 2 (N = 12), there was an average of 1792+/-99 (CV = 0.05) nerve fibers. The average percentage of small, medium and large size fibers was 22%, 51.2% and 26.8%. In the macula utricle from group 1, there was an average of 3026 nerve fibers (N = 2, ages 80 and 96 years old). There was an average 30.75% small, 56% medium and 13.2% large size fibers. In the utricular macula from group 2 (N = 3, ages 84, 92 and 96 years old), there was an average of 3715 nerve fibers. The average percentage of small, medium and large size fibers was 33.2%, 51.7% and 15.1%. The nerve fiber number in both groups is within the range of previous studies, however, the number of fibers in group 2 was significantly higher than that in group 1 (p = 0.01). This difference is likely due to increased sensitivity gained by the immunohistochemical staining of the axoplasm of nerve fibers in group 2. Results from the present study demonstrate the use of unbiased stereology and immunohistochemistry in human vestibular endorgans, as a reliable and efficient method to estimate the number of nerve fibers. These methods can be applied for studies of normal aging and pathological conditions of the vestibular periphery.

Histopathological and ultrastructural analysis of vestibular endorgans in Meniere's disease reveals basement membrane pathology

BackgroundWe report the systematic analysis of the ultrastructural and cytological histopathology of vestibular endorgans acquired from labyrinthectomy in Menieres disease.Methods17 subjects with intractable Menieres disease and ipsilateral non-serviceable hearing presenting to the Neurotology Clinic from 1997 to 2006 who chose ablative labyrinthectomy (average age = 62 years; range 29–83 years) participated. The average duration of symptoms prior to surgery was 7 years (range 1–20 years).ResultsNearly all vestibular endorgans demonstrated varying degrees of degeneration. A monolayer of epithelial cells occurred significantly more frequently in the horizontal cristae (12/13 = 92%) (p < 0.001), the superior cristae (5/5 = 100%) (p < 0.005), the posterior cristae (2/2) compared with the utricular maculae (4/17 = 24%). Basement membrane (BM) thickening was more common in all of the cristae ampullares (18 out of 20) than the utricular maculae. Although only four saccular maculae were obtained, 3 out of 4 exhibited BM thickening and monolayer degeneration. Monolayer degeneration was highly significantly correlated with the presence of BM thickening (p < 0.001). Other degenerative changes noted equally among the five vestibular endorgans which were not significantly correlated with BM thickening or monolayer degeneration included hair cell vacuolization and stereocilia loss, microvesicles in the supporting cells, and increased stromal intercellular spaces. Transmission electron microscopy demonstrated disorganization of the BM collagen-like fibrils, and normal ultrastructural morphology of the nerve terminals and myelinated fibers. Stromal fibroblasts and endothelial cells of stromal blood vessels demonstrated vacuolization, and stromal perivascular BMs were also thickened.ConclusionSystematic histopathological analysis of the vestibular endorgans from Menieres disease demonstrated neuroepithelial degeneration which was highly correlated with an associated BM thickening. Other findings included hair cell and supporting cell microvessicles, increased intercellular clear spaces in the stroma, and endothelial cell vacuolization and stromal perivascular BM thickening.

Immunolocalization of voltage-gated calcium channel α1 subunits in the chinchilla cochlea

The immunohistochemical localization of α1A, α1B, α1C, α1D, and α1E voltage-gated calcium channel subunits was investigated in the chinchilla organ of Corti and spiral ganglia with the use of specific antipeptide antibodies. The inner and outer hair cells were immunoreactive for α1A and α1D subunit antibodies. α1C immunoreactivity localized to the nerve terminals innervating inner hair cells and the basal pole of the outer hair cell. There was only non-specific staining to α1B and α1E. Supporting cells were non-immunoreactive. Spiral ganglia neurons were α1B, α1C, and α1D immunoreactive. A few spiral ganglia neurons were α1E immunoreactive. The importance of α1D, the pore-forming subunit of the L-type channel, in outer and inner hair cell function has been clearly demonstrated in electrophysiological, molecular biological, and knockout models. The presence of α1A, the pore-forming subunit of the P/Q type channels, has not previously been demonstrated in inner and outer hair cells, and its function in the cochlear hair cell is unknown.