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.

Alpha-defensin overexpression in patients with Bell's palsy and Ramsay Hunt syndrome.

OBJECTIVES: To investigate the biological factors related to the onset of Bell's palsy, we sought to identify differentially expressed genes in peripheral blood mononuclear cells (PBMCs) and plasma of patients with Bell's palsy and Ramsay Hunt syndrome (RHS). METHODS: We carried out DNA microarray analyses using PBMCs taken from patients with Bell's palsy at their initial visit and 2 to 4 weeks later. To validate these analyses, we measured the relative messenger RNA levels of alpha-defensin in paired PBMCs by reverse transcription-polymerase chain reaction. The plasma concentrations of alpha-defensin in patients and healthy volunteers were quantified by enzyme-linked immunosorbent assay. RESULTS: The DNA microarray analysis identified alpha-defensin as a candidate gene related to the onset of Bell's palsy. Reverse transcription-polymerase chain reaction analysis showed that the relative alpha-defensin messenger RNA levels in PBMCs from the later visit were increased at least twofold in 9 of 13 patients (69%) with Bell's palsy and in 4 of 6 patients (67%) with RHS. The plasma alpha-defensin concentrations in the patients with RHS were significantly higher than those in healthy volunteers (p = 0.0013) and in the patients with Bell's palsy (p = 0.0306). Elevations of plasma alpha-defensin were observed in 5 of the 9 patients with Bell's palsy who demonstrated alpha-defensin overexpression in PBMCs. CONCLUSIONS: alpha-Defensin may be one of the biological factors related to the onset of Bell's palsy and RHS.

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.

[Hearing loss of aging].

The gradual hearing loss is seen in every people as they get older. In this symposium, anatomy and physiology of the ear were talked at first. Next, diseases which cause hearing disturbance were explained. Especially, we focused on the age-related hearing loss. It was emphasized that we should speak to elderly people very slowly and clearly so that they could understand us well. At last, the usefulness and progress of hearing aids were introduced. It is very important to tune their hearing aids to the individual. We hope that this symposium would help the attendance to enjoy every day of their lives.

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.

Activity changes in monkey superior colliculus during saccade adaptation.

Saccades are eye movements that are used to foveate targets rapidly and accurately. Their amplitude must be adjusted continually, throughout life, to compensate for movement inaccuracies due to maturation, pathology, or aging. One possible locus for such saccade adaptation is the superior colliculus (SC), the relay for cortical commands to the premotor brain stem generator for saccades. However, previous stimulation and recording studies have disagreed as to whether saccade adaptation occurs up- or downstream of the SC. Therefore we have reexamined the behavior of SC burst neurons during saccade adaptation under conditions that were optimized to produce the biggest possible change in neuronal activity. We show that behavioral adaptation of saccade amplitude was associated with significant increases or decreases, in the number of spikes in the burst and/or changes in the shape of the movement field in 35 of 43 SC neurons tested. Of the 35, 29 had closed movement fields and 14 were classified indeterminate because the movement field could not be definitively diagnosed. Changes in the number of spikes occurred gradually during adaptation and resulted from correlated changes in burst lead and duration without consistent changes in peak burst rate. These data indicate that the great majority of SC neurons show a change in discharge in association with saccade amplitude adaptation. Based on these and previous results, we speculate that the site for saccade adaptation resides in the SC or that the SC is the final common pathway for adaptive changes that occur elsewhere in the saccade system.

Pursuit-related neurons in the supplementary eye fields: discharge during pursuit and passive whole body rotation.

The primate frontal cortex contains two areas related to smooth-pursuit: the frontal eye fields (FEFs) and supplementary eye fields (SEFs). To distinguish the specific role of the SEFs in pursuit, we examined discharge of a total of 89 pursuit-related neurons that showed consistent modulation when head-stabilized Japanese monkeys pursued a spot moving sinusoidally in fronto-parallel planes and/or in depth and with or without passive whole body rotation. During smooth-pursuit at different frequencies, 43% of the neurons tested (17/40) exhibited discharge amplitude of modulation linearly correlated with eye velocity. During cancellation of the vestibulo-ocular reflex and/or chair rotation in complete darkness, the majority of neurons tested (91% = 30/33) responded. However, only 17% of the responding neurons (4/30) were modulated in proportion to gaze (eye-in-space) velocity during pursuit-vestibular interactions. When the monkeys fixated a stationary spot, 20% of neurons tested (7/34) responded to motion of a second spot. Among the neurons tested for both smooth-pursuit and vergence tracking (n = 56), 27% (15/56) discharged during both, 62% (35/56) responded during smooth-pursuit only, and 11% (6/56) during vergence tracking only. Phase shifts (relative to stimulus velocity) of responding neurons during pursuit in frontal and depth planes and during chair rotation remained virtually constant (< or =1 Hz). These results, together with the robust vestibular-related discharge of most SEF neurons, show that the discharge of the majority of SEF pursuit-related neurons is quite distinct from that of caudal FEF neurons in identical task conditions, suggesting that the two areas are involved in different aspects of pursuit-vestibular interactions including predictive pursuit.

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.

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

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.