Norihito Takeichi

Fractionated stereotactic radiotherapy for vestibular schwannoma (VS): Comparison between cystic-type and solid-type VS

PURPOSE To compare the effectiveness and complications of fractionated stereotactic radiotherapy (SRT) for cystic-type vestibular schwannoma (VS) with those of solid-type VS. METHODS AND MATERIALS In 65 patients treated with fractionated SRT between 1991 and 1999, 20 were diagnosed with cystic VS, in which at least one-third of the tumor volume was a cystic component on magnetic resonance imaging (MRI), and 45 were diagnosed with solid VS. Thirty-six Gy to 50 Gy in 20-25 fractions was administered to the isocenter and approximately 80% of the periphery of the tumor. All cystic and solid components were included in the gross tumor volume. The mean follow-up period was 37 months, ranging from 6 to 97 months. RESULTS The actuarial 3-year rate of no episode of enlargement greater than 2.0 mm was 55% for cystic-type and 75% for solid-type VS; the difference was statistically significant (p = 0.023). The actuarial 3-year tumor-reduction (reduction in tumor size greater than 2.0 mm) rates were 93% and 31%, respectively (p = 0.0006). The overall actuarial tumor control rate (no tumor growth greater than 2. 0 mm after 2 years or no requirement of salvage surgery) was 92% at 5 years in 44 patients with a follow-up period of 2 or more years. There was no difference in the class hearing preservation rate between cystic VS and solid VS. No permanent trigeminal or facial nerve palsy was observed in either group. CONCLUSION Transient tumor enlargement occurs in cystic VS more frequently than in solid-type VS, but the subsequent tumor-reduction rate in cystic VS is better.

Positional vertigo and macroscopic downbeat positioning nystagmus in spinocerebellar ataxia type 6 (SCA6)

Abstract. To investigate the frequency of positioning nystagmus in degenerative ataxic disorders, we examined downbeat positioning nystagmus (DPN) in 25 patients with spinocerebellar ataxia type 6 (SCA6) and 58 patients with other types of degenerative ataxia. DPN was observed in 21 of the 25 patients with SCA6 (84 %) versus only 3 of the 58 patients (5.2 %) with other types of degenerative ataxia, including multiple system atrophy, SCA1, SCA2, SCA3/Machado-Joseph disease, and non-SCA6 late-onset pure cerebellar ataxia. Our findings indicated that DPN is a distinct part of the clinical presentation of SCA6, showing that vestibular cerebellum is more affected in SCA6 than other types of degenerative ataxia.

Vestibular evoked myogenic potential (VEMP) in patients with acoustic neuromas

OBJECTIVE To study the utility of VEMP (vestibular-evoked myogenic potential) in the diagnosis of acoustic neuromas. METHODS Eighteen patients with unilateral acoustic neuromas were subjected to this study. Myogenic potential responding to loud click stimuli was recorded at ipsilateral sternocleidomastoid muscle. A normal range of VEMP was obtained from 20 controls. VEMP responses were compared with both, clinical symptoms and results of caloric tests. RESULT Thirteen out of 18 patients showed decreased responses of VEMP at the affected side. VEMP responses seemed to have little relation with dysequilibrium, spontaneous nystagmus, canal paresis and pure-tone hearing. CONCLUSION VEMP is useful for detecting dysfunction of inferior vestibular nerve in patients with acoustic neuromas.

Annual rate of hearing loss falls after fractionated stereotactic irradiation for vestibular schwannoma

PURPOSE The rate of hearing loss in a population before and after irradiation was investigated to determine the effect of irradiation on hearing impairment. METHODS AND MATERIALS In 72 patients with vestibular schwannoma who received fractionated stereotactic irradiation from 1992 to 1999, 21 had had their hearing levels examined 3 months or more before the treatment. The mean time between the initial examination and treatment was 18.6 months (range: 3-89 months), and the mean time between treatment and the last follow-up was 24.2 months (12-69 months). Thirty-six to 50 Gy in 20-25 fractions over 5 to 6 weeks was given using an X-ray beam from a linear accelerator. Pure tone average (PTA) was measured using the mean hearing level at five frequencies, and the annual rate of hearing loss was defined as [(hearing loss in PTA(dB))/(follow-up period (months)x12)]. RESULTS The actual cumulative curve of decrease in tumor size of 2 mm or more was 38.3% at 2 years and 80.0% at 3 years. The mean of hearing loss in PTA was 11.6+/-10.3 dB (-1 to 35 dB) from the initial examination to the start of irradiation and 11.9+/-14.4 dB (-14 to 37 dB) from the start of irradiation to the last follow-up. The mean annual rates of hearing loss before irradiation and in the 1st,2nd,3rd and 4th years after irradiation were, respectively, 18.6, 11.2, 6.2, 5.1, and 5.0 dB/year. The annual rates of hearing loss in the 2nd year (P=0.025) and 3rd year (P=0.018) were significantly slower than the rate before irradiation. CONCLUSIONS The mean annual rate of hearing loss was higher before irradiation than after irradiation, and hearing loss slowed rather than accelerated after irradiation. Although hearing loss after the treatment was usually permanent, fractionated stereotactic irradiation was suggested to be effective to lower the rate of hearing loss.

Neurons in the Caudal Frontal Eye Fields of Monkeys Signal Three‐Dimensional Tracking

To maintain optimal clarity of objects moving in three dimensions, precise coordination of binocular eye movements is required in frontal‐eyed primates. Caudal parts of the frontal eye fields (FEFs) contain smooth pursuit neurons and the discharge of the majority of them is related to vergence eye movements as well. However, whether or not those pursuit neurons carry true binocular signals has not been tested critically. Using dichoptic stimuli that dissociate horizontal movements of the left and right eyes, we found that all pursuit‐related, FEF neurons tested carried binocular signals.

Olfactory epithelium consisting of supporting cells and horizontal basal cells in the posterior nasal cavity of mice

Abstract. The olfactory epithelium of mice generally consists of olfactory cells, progenitors of olfactory cells (globose basal cells), supporting cells, and horizontal basal cells. However, in the dorsal fossa (the roof) of the posterior nasal cavity of mice, we found seven epithelial patches consisting of only non-neuronal cell types, i.e., supporting cells and horizontal basal cells, among the normal olfactory epithelium. The supporting cells occupied three or four layers in the apical to middle regions; in the basal region, horizontal basal cells were localized in a single row adjacent to the basement membrane. Bowmans gland ducts were also present in the epithelium. Neuronal cells (olfactory cells and globose basal cells) were totally absent. The ultrastructure of the supporting cells, horizontal basal cells, and Bowmans glands was essentially similar to that in the normal olfactory epithelium. In the early postnatal period (P1–P7), cell types in the epithelium were the same as those in the normal olfactory epithelium. From P10 to P21, olfactory cells and globose basal cells had disappeared from the olfactory epithelium. At this period, the number of TUNEL-positive cells was significantly higher than that in the surrounding olfactory epithelium; ultrastructurally, many apoptotic figures were observed. This suggests that the epithelium consisting of supporting cells and horizontal basal cells is generated by the apoptotic death of olfactory cells and globose basal cells during postnatal development.

Symptomatic Outcomes in Relation to Tumor Expansion After Fractionated Stereotactic Radiation Therapy for Vestibular Schwannomas: Single-Institutional Long-Term Experience

PURPOSE The effect of transient tumor expansion after conventionally fractionated stereotactic radiation therapy (SRT) on the symptomatic outcomes is not well-known. METHODS AND MATERIALS This study enrolled 201 consecutive patients who received SRT for vestibular schwannoma. A conventional fractionation schedule was applied in 194 patients (97%), and 142 (71%) received a total dose of 50 Gy. The median follow-up time was 72 months. RESULTS The maximum diameter was 9 mm or less in 13 patients, 10-19 mm in 79 patients, 20-29 mm in 87 patients, and 30 mm or greater in 22 patients. At presentation, tumor size of 20 mm or greater was significantly associated with loss of serviceable hearing and trigeminal neuropathy. After SRT, tumor expansion was observed in 42 patients (21%). By tumor size, tumor expansion was observed in 0%, 11.4%, 25.6%, and 50% of patients with tumors of 9 mm or less, 10-19 mm, 20-29 mm, and 30 mm or greater, respectively, in diameter. The tumor expansion was significantly associated with an increased risk of hydrocephalus requiring shunt placement (P=.004), loss of serviceable hearing (P=.0064), and worsening of facial (P<.0001) and trigeminal nerve (P<.0001) functions. Spontaneous tumor shrinkage was observed in 29 of those 42 patients, mostly within 2 years after the expansion, and the majority of the worsened symptoms except for hearing resolved once the tumor had shrunk. As a result, salvage surgical resection for symptomatic relief was required in only 5% of patients. CONCLUSIONS Fractionated SRT could be safely applied even for medium- to large-sized (≥20 mm) tumors. However, greater knowledge of the risks and consequences, including transient symptomatic worsening, and the time span of expansion will be required for the follow-up of patients after SRT to avoid unnecessary surgical intervention.

TECTA mutations in Japanese with mid-frequency hearing loss affected by zona pellucida domain protein secretion

TECTA gene encodes α-tectorin, the major component of noncollagenous glycoprotein of the tectorial membrane, and has a role in intracochlear sound transmission. The TECTA mutations are one of the most frequent causes of autosomal dominant (AD) hearing loss and genotype–phenotype correlations are associated with mutations of TECTA in exons according to α-tectorin domains. In this study, we investigated the prevalence of hearing loss caused by TECTA mutations in Japanese AD hearing loss families, and confirmed genotype–phenotype correlation, as well as the intracellular localization of missense mutations in the α-tectorin domain. TECTA mutations were detected in 2.9% (4/139) of our Japanese AD hearing loss families, with the prevalence in moderate hearing loss being 7.7% (4/52), and all patients showed typical genotype–phenotype correlations as previously described. The present in vitro study showed differences of localization patterns between wild type and mutants, and suggested that each missense mutation may lead to a lack of assembly of secretion, and may reduce the incorporation of α-tectorin into the tectorial membrane.

Involvement of the Frontal Oculomotor Areas in Developmental Compensation for the Directional Asymmetry in Smooth‐Pursuit Eye Movements in Young Primates

The smooth pursuit system moves the eyes in space to accurately track objects of interest and maintain their images on the foveae while compensating for conflicting visual inputs from the moving background and/or vestibular inputs during head movements. Under demanding task conditions, young (but not mature) primates have difficulty with upward smooth gaze (eye in space) movement; pursuit breaks down, and they perform the task with saccades. Proper compensation matures later, after preadolescence. Chemical inactivation of the supplementary eye fields in compensated monkeys reproduced the directional asymmetry that had been compensated developmentally, suggesting that the supplemental eye fields may be involved in the compensation.

Downbeat positioning nystagmus is a common clinical feature despite variable phenotypes in an FHM1 family

Clinical examinations and mutational analyses were carried out in three patients of a Japanese familial hemiplegic migraine (FHM) pedigree. Each affected member demonstrated a broad clinical spectrum that included hemiplegic migraine with progressive cerebellar ataxia, migraine without aura, and episodic ataxia. Despite this variability, all members exhibited marked downbeat positioning nystagmus, and magnetic resonance images (MRI) all showed cerebellar atrophy predominantly of the cerebellar vermis. All affected members had a T666M missense mutation in the protein encoded by the CACNA1A gene (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit). Although clinical features associated with the T666M CACNA1A mutation are highly variable, downbeat positioning nystagmus may be an important clinical feature of this disease.