Poly-S-nitrosated human albumin enhances the antitumor and antimetastasis effect of bevacizumab, partly by inhibiting autophagy through the generation of nitric oxide.

Autophagy is one of the major causes of drug resistance. For example, the angiogenesis inhibitor bevacizumab shows only transient and short-term therapeutic effects, whereas long-term therapeutic benefits are rarely observed, probably due to hypoxia-induced autophagy. Nitric oxide (NO) is an important molecule with multiple functions, and it has recently been reported to function as a regulator of autophagy. Therefore, a reasonable therapeutic strategy for overcoming drug resistance by NO would involve it being directly delivered to the tumor. Here, we investigated the inhibitory effect of NO on autophagy by using a macromolecular NO donor S-nitrosated human serum albumin (SNO-HSA) with a high degree of NO loading and tumor targeting potential. In colon 26 (C26) cells, SNO-HSA significantly suppressed hypoxia-induced autophagy by inhibiting the phosphorylation of JNK1 and the expression of its downstream molecule Beclin1. The effect of SNO-HSA was also confirmed in vivo by combining it with Bev. In C26-bearing mice, significant suppression of tumor growth as well as lung metastasis was achieved in the combination group compared to the SNO-HSA or bevacizumab alone group. Similar to the in vitro experiments, the immunostaining of tumor tissues clearly showed that SNO-HSA inhibited the autophagy of tumor cells induced by bevacizumab treatment. In addition to other known antitumor effects of SNO-HSA, that is, the induction of apoptosis and the inhibition of multidrug efflux pumps, these data may open alternate strategies for cancer chemotherapy by taking advantage of the ability of SNO-HSA to suppress autophagy-mediated drug resistance and enhance the efficacy of chemotherapy.

Polyion complex vesicles for photoinduced intracellular delivery of amphiphilic photosensitizer.

Polymer vesicles formed by a pair of oppositely charged poly(ethylene glycol) (PEG)-based block aniomer and homocatiomer, termed "PICsomes", have tunable size, and are characterized by unique semipermeable property due to the flexible and tunable hydrophilicity of polyion complex (PIC) membranes. The PICsomes can encapsulate a variety of molecules in an inner aqueous phase just by a simple vortex mixing of solution, expecting their utility as nanocontainers of substances with biomedical interests. Here, we report on a new functionality of the PICsomes: photoinduced release of photoactive agents for intracellular drug delivery. A potent photosensitizer, Al(III) phthalocyanine chloride disulfonic acid (AlPcS2a), was efficiently incorporated into the PICsomes (11%(w/w)), and its quick release was induced by photoirradiation possibly due to the photochemical damage of the PIC membranes. The combination of a high-resolution fluorescent confocal microscopy and a lysosome membrane-specific staining method revealed that such photoinduced release of AlPcS2a occurred even in the lysosomes of living cells after endocytic internalization. Simultaneously, the released AlPcS2a photochemically affected the integrity of the lysosomal membranes, leading to the translocation of AlPcS2a and PICsomes themselves to the cytoplasm. Consequently, the AlPcS2a-encapsulated PICsomes (AlPcS2a-PICsomes) exhibited appreciably stronger photocytotoxicity compared with free AlPcS2a alone. Thus, the AlPcS2a-PICsomes have promising feasibility for the photodynamic therapy or the photoinduced cytoplasmic delivery of therapeutic molecules.

Developmental changes in the protective effect of exogenous brain-derived neurotrophic factor and neurotrophin-3 against ototoxic drugs in cultured rat vestibular ganglion neurons.

We examine developmental changes in the responsiveness of rat vestibular ganglion neurons (VGNs) to two neurotrophic factors (NTFs), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and investigate the protective effects of these NTFs against ototoxic drugs during postnatal development in dissociated cultures. VGNs were obtained from rats on postnatal days (P) 1, 3, 7 and 14. BDNF facilitated neuronal survival as well as neurite sprouting of VGNs obtained from younger rats (P1 and P3), whereas these effects were not observed in older rats (P7 and P14). BDNF was also effective in facilitating neurite extension in VGNs at each of the postnatal ages. NT-3 also facilitated neuronal survival and neurite extension of VGNs from younger rats but these effects were significantly smaller than those of BDNF (p < 0.05). The protective effects of BDNF and NT-3 against ototoxic drugs, gentamicin and cisplatin, were also age-dependent: they were effective for neuronal survival, neurite sprouting and neurite extension in VGNs from younger rats, whereas these effects tended to disappear in VGNs from older rats. Analysis of the changes in the expression of the receptors of NTFs revealed that expression of TrkB and TrkC proteins and their mRNA did not change during the developmental period, whereas expression of p75(NTR) protein was down-regulated together with that of p75(NTR) mRNA during the developmental period. Developmental changes in the responsiveness to exogenous NTFs in VGNs, which is not caused by the changes of their receptors but probably caused by changes in the intracellular signaling pathways, should be taken into consideration in the prevention of neuronal degeneration caused by ototoxic drugs.

Estimated incidence and characteristics of vestibular neuritis in Japan: A nationwide survey.

OBJECTIVE: To assess the annual incidence of vestibular neuritis (VN) in the Japanese population. METHODS: We conducted a mail-based survey targeting otolaryngologic clinics and hospitals across Japan to estimate the annual number of patients who were newly-diagnosed with VN during the one-year period of 2021. Using a stratified sampling method, we selected 1,107 departments and asked them to report the number of new patients with VN and their demographics. The total number of VN patients was estimated by multiplying the reported numbers by the reciprocal of the sampling rate and response rate. RESULTS: The overall survey response rate was 40.5 % (448 departments). The estimated number of newly-diagnosed VN patients in 2021 was 8,861 (95 % confidential interval [CI], 2,290-15,432) The annual incidence of VN was 7.05 per 100,000 population in Japan. The male-to-female ratio of VN patients was 0.96, and the mean age was 60.3 ± 16.1 years (range 11-94 years). CONCLUSIONS: The annual incidence of VN in Japan in 2021 had almost doubled and the mean age had become older compared to the previous study in 1993 (annual incidence; 3.5 per 100,000 per year; mean age: 45 years).

Effect of vestibular dysfunction on the development of gross motor function in children with profound hearing loss.

OBJECTIVE: To evaluate the function of the superior and inferior vestibular nerve systems in children with profound sensorineural hearing loss, and to assess the influence of dysfunction of each vestibular nerve system on the development of gross motor function. STUDY DESIGN: Retrospective study. SETTING: A tertiary referral center. METHODS: Eighty-nine children (age range: 20-97 months) with profound sensorineural hearing loss who were due to undergo cochlear implant surgery were recruited. Function of the superior vestibular nerve system was evaluated by the damped rotation test and the caloric test, whereas functions of the inferior vestibular nerve systems were evaluated by the vestibular evoked myogenic potential (VEMP) test. Gross motor development was assessed using the age of acquisition of head control and independent walking. RESULTS: Among the children able to complete the vestibular function tests, abnormalities were found in 20% (16 of 84 children) in the damped rotation test, 41% (31 of 75 children) in the caloric test and 42% (26 of 62 children) in the VEMP test. Children who showed abnormal responses in the vestibular function tests showed significantly delayed acquisition of head control (p < 0.05) and independent walking (p < 0.05) in comparison with children with normal responses. The children who showed abnormal responses in all 3 vestibular tests showed the greatest delay in acquisition of gross motor function in comparison with the other groups. CONCLUSIONS: Children with profound hearing loss tend to have dysfunction in the superior as well as the inferior vestibular nerve systems. Both the superior and inferior vestibular nerve systems are important for the development of gross motor function in children.

Diagnostic usefulness of multifrequency tympanometry for Ménière's disease.

Multifrequency tympanometry (MFT) is the measurement of the impedance of the middle ear transmission system at a wide range of frequencies from 200 Hz to 2 kHz. A potential use of MFT as a new diagnostic tool for detecting endolymphatic hydrops has recently been reported. However, its clinical usefulness for diagnosing Ménière's disease (MD) remains unclear. To evaluate the clinical usefulness of MFT as a new qualitative and diagnostic test for MD, we performed MFT in 70 patients with unilateral or bilateral MD and in 29 normal control subjects. The width of double peaks in the admittance tympanograms (Y width) at 2 kHz and the resonance frequency (RF) were analyzed, and receiver operating characteristic (ROC) curves were constructed. The Y width in MD-affected ears was significantly greater than that in control ears (p < 0.001). The RF in MD-affected ears was significantly lower than that in control ears (p < 0.01). Neither the Y width nor RF had a significant relationship with hearing levels or the results of caloric and vestibular myogenic potential testings. The area under the ROC curve was 0.71 for the Y width and 0.66 for the RF. At the optimal cutoff points, the sensitivity and specificity of the Y width were 47.3 and 86.8%, respectively, and those of the RF were 41.3 and 84.2%, respectively. These results indicated that MFT is significantly associated with the presence of MD, but its diagnostic accuracy is only modest. MFT is a simple, noninvasive test, which should be considered as a complementary test in the diagnosis of MD.

Progression of Peripheral Vestibular Dysfunctions in Patients With a Mitochondrial A3243G Mutation.

OBJECTIVE: To evaluate the progression of peripheral vestibular dysfunction in patients with an A-to-G point mutation at nucleotide pair 3243 in mitochondrial DNA (A3243G mutation). STUDY DESIGN: Retrospective patient series. SETTING: Tertiary referral center. PATIENTS: Six unrelated patients with an A3243G mutation (four mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; and two maternally inherited diabetes and deafness; five females and one male; average age 41 ±â€Š11.3 yr old), who underwent repeated vestibular examinations, were included (average interval between the first and second examinations: 5.7 ±â€Š2.1 yr). INTERVENTION: Diagnostic. MAIN OUTCOME MEASURE: Results of caloric testing and cervical vestibular evoked myogenic potential testing in response to air-conducted sound were analyzed. RESULTS: All the patients except one, who was already completely deaf in both ears at the first examination, showed progression of hearing loss (average 4.0 ±â€Š6.3 dB per year). Five of the six patients had vestibular symptoms at the first examination. The other patient developed dizziness later. Caloric responses were abnormal in four patients at the first examination and in five patients at the second examination. Cervical vestibular evoked myogenic potential responses were bilaterally absent in three patients at the first examination and in five patients at the second examination. CONCLUSIONS: The A3243G mutation causes progression of peripheral vestibular dysfunction as well as that of hearing loss.

Surgical treatment of substernal goiter: An analysis of 44 cases.

OBJECTIVE: Substernal goiters are classified as primary or secondary intrathoracic goiters. Here, we report the diagnosis, symptoms, treatment, and postoperative complications of 44 substernal goiters (2 primary mediastinal goiter and 42 secondary mediastinal goiters). METHODS: A retrospective chart review of 351 patients undergoing thyroidectomy at the Department of Otolaryngology-Head and Neck Surgery of the Tokyo Metropolitan Tama Medical Center. Between 2009 and 2015, 44 patients underwent surgery for substernal goiter. RESULTS: The frequency of primary and secondary mediastinal goiters was 0.5% and 11.9%, respectively. The preoperative symptoms were neck mass, dyspnea, and dysphagia. Eight patients were asymptomatic. Thirty-nine patients had benign masses and 5 patients had malignant masses. Most patients were operated on for adenomatous goiters (52.2%). In ten cases beyond the aortic arch, the tumors were benign and there were eight cases of adenomatous goiter. All patients underwent a successful transcervical incision without sternotomy. Even the primary intrathoracic goiters were extracted after total thyroidectomy via the cervical approach without complications. Although one case showed unilateral recurrent nerve paralysis as a postoperative complication, phonetic function improved in 6 postoperative months. No instances of postoperative bleeding or definitive hypoparathyroidism occurred, and tracheostomy was not performed in any of the cases. CONCLUSION: The cervical approach was safely performed in almost all substernal goiters without an extracervical procedure. Selected cases of primary mediastinal goiter may be excised via the cervical approach.

Vestibular Evoked Myogenic Potentials in Vestibular Migraine: Do They Help Differentiating From Menière's Disease?

OBJECTIVE: To investigate whether both cervical and ocular vestibular myogenic potentials (cVEMPs and oVEMPs) to air-conducted sound (ACS) and bone-conducted vibration (BCV) can help to differentiate vestibular migraine (VM) and Menière's disease (MD). STUDY DESIGN: Retrospective study. SETTINGS: A tertiary referral center. SUBJECTS AND METHODS: Twenty-eight patients with VM, 28 patients with definite unilateral MD, and 28 age-matched controls were included. Cervical VEMPs to 500 Hz ACS (cVEMPs-air) and 500 Hz BCV (cVEMPs-bone), oVEMPs to 500 Hz ACS (oVEMPs-air) and 500 Hz BCV (oVEMPs-bone), and caloric tests were performed. Results of these vestibular function tests were compared between the groups. RESULTS: The prevalence of abnormality was significantly higher in VM than in controls only for the caloric test (P < .05). Asymmetry ratios (ARs) for cVEMPs-air and oVEMPs-air were significantly larger in VM than in controls (P < .05). Between VM and MD, the prevalence of abnormality was significantly different only for oVEMPs-air. The ARs for oVEMPs-air and caloric test asymmetries were significantly smaller in VM than in MD (P < .05). CONCLUSIONS: Among the vestibular function tests, oVEMPs-air may be most helpful for the differentiation of VM from MD as a group.

A clinical review of 38 cases of cervical tuberculous lymphadenitis in Japan - The role of neck dissection.

OBJECTIVES: After tuberculous pleurisy, lymphadenitis arising from cervical lesion is the second most common form of extrapulmonary tuberculosis. It is generally treated with antituberculosis agents, but some patients resist chemotherapy. In such cases, surgical resection is often considered as an alternative treatment. This study aims to evaluate the therapeutic outcome of cervical tuberculous lymphadenitis and the future course of treatment of this disease. METHODS: We retrospectively reviewed the clinical charts of patients diagnosed at the Tokyo Metropolitan Tama Medical Center between 2009 and 2015 and identified 38 cases of cervical tuberculous lymphadenitis. Precisely 798 patients were registered for primary tuberculosis at our institution during the same period. RESULTS: Patient ages ranged from 21 to 85 years (average: 58.9 years), and the male-to-female ratio was 1:1.2. The range of tuberculosis progression was as follows: 30 (78.9%) in only the cervical lymph node, 3 in the other (axillary, mediastinal, and abdominal) lymph nodes, 1 in the lung and vertebrae lumbales, 2 in the lung, and 1 in the pleural membrane. All 38 patients were initially treated with antituberculous drugs at the Department of Pulmonary Medicine based on guidelines for tuberculosis cases in Japan. In seven cases, the antituberculous drugs were replaced due to side effects. Four cases involved a single drug-resistant strain, and one case involved a double drug-resistant strain. Thirty-three (86.8%) cases were cured by chemotherapy alone. The three patients resistant to chemotherapy were successfully treated through neck dissection. Thirty-six cases (94.7%) were cured by chemotherapy or chemotherapy and surgery. CONCLUSION: Local therapy could prove effective in cervical tuberculous lymphadenitis patients who exhibit an inadequate response to drugs. The role of neck dissection in cervical tuberculous lymphadenitis remains an important consideration.

Calcium phosphate-based organic-inorganic hybrid nanocarriers with pH-responsive on/off switch for photodynamic therapy.

Photodynamic therapy (PDT) is a promising treatment modality for malignant tumors in a light-selective manner. To improve the PDT efficacy, numerous kinds of nanocarriers have been developed to deliver photosensitizers (PSs) selectively into the tumor through leaky tumor-associated vasculature. However, the corresponding prolonged retention of the nanocarrier in the bloodstream may lead to unfavorable photochemical damage to normal tissues such as skin. Here, we report an organic-inorganic hybrid nanocarrier with a pH-responsive on/off switch of PDT efficacy. This hybrid nanocarrier is constructed by hydrothermal synthesis after simple mixing of calcium/phosphate ions, chlorin e6 (amphiphilic low molecular weight PS), and poly(ethylene glycol)-b-poly(aspartic acid) (PEG-PAsp) copolymers in an aqueous solution. The hybrid nanocarrier possesses a calcium phosphate (CaP) core encapsulating the PSs, which is surrounded by a PEG shielding layer. Under physiological conditions (pH 7.4), the nanocarrier suppressed the photochemical activity of PS by lowering the access of oxygen molecules to the incorporated PS, while PDT efficacy was restored in a pH-responsive manner because of the dissolution of CaP and eventual recovery of access between the oxygen and the PS. Owing to this switch, the nanocarrier reduced the photochemical damage in the bloodstream, while it induced effective PDT efficacy inside the tumor cell in response to the acidic conditions of the endo-/lysosomes.

Ocular vestibular evoked myogenic potential elicited from binaural air-conducted stimulations: clinical feasibility in patients with peripheral vestibular dysfunction.

CONCLUSION: Ocular vestibular evoked myogenic potentials (oVEMPs) to binaural air-conducted stimulation (ACS) may provide a convenient way of assessing the crossed vestibulo-ocular reflex in patients with vestibular dysfunction as well as in healthy subjects. OBJECTIVE: To investigate the clinical feasibility of using oVEMPs in response to binaural ACS to assess normal subjects and patients with vestibular dysfunction. METHODS: The study investigated 24 normal subjects (14 men and 10 women, aged from 23 to 60 years) and 14 patients with unilateral peripheral vestibular dysfunction. Each subject underwent oVEMP testing in response to monaural ACS and binaural ACS (500 Hz tone burst, 135 dBSPL). RESULTS: In normal subjects, bilateral oVEMPs were elicited in 75% of subjects in response to monaural ACS and in 91% in response to binaural ACS. Asymmetry ratios (ARs) of the responses to binaural ACS were significantly smaller than those of the responses to monaural ACS (p < 0.01). In patients with unilateral vestibular dysfunction, there were no significant differences in the amplitude, latency, or AR of the responses between monaural and binaural ACS. Approximately 30% of patients showed reduced ARs to binaural ACS relative to monaural ACS, primarily due to contamination by uncrossed responses elicited in healthy ears.

Ocular vestibular evoked myogenic potentials in response to air-conducted sound and bone-conducted vibration in vestibular schwannoma.

OBJECTIVE: To clarify the origin and pathways of ocular vestibular evoked myogenic potentials (oVEMPs) to air-conducted sound (ACS), we compared the results of oVEMPs with ACS, with oVEMPs with bone-conducted vibration (BCV), cervical VEMPs (cVEMPs) with ACS, and the caloric test in patients with unilateral vestibular schwannoma (VS). STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Forty-five patients with untreated unilateral VS. MAIN OUTCOME MEASURE: Each patient underwent vestibular tests, including oVEMPs to ACS, oVEMPs to BCV, cVEMPs to ACS, and caloric tests. The correlations among these tests were evaluated. RESULTS: Of the 45 patients recruited, 28 patients (63%) showed reduced or absent oVEMPs to ACS solely on the affected side. There were no significant differences in abnormal response ratios among oVEMPs to ACS, oVEMPs to BCV, cVEMPs to ACS, or the caloric test. The results of oVEMPs to ACS had a significant correlation with those of oVEMPs to BCV and the caloric test (p < 0.05) but not with those of cVEMPs to ACS (p > 0.05). CONCLUSION: These findings support the hypothesis that oVEMP in response to ACS are predominantly mediated by the superior vestibular nerve and probably reflect the function of the utricle.

Developmental changes in the expression of Κv1 potassium channels in rat vestibular ganglion cells.

The primary afferent neurons of the vestibular ganglion convey sensory information from hair cells in the semicircular canals and otolith organs to the vestibular nuclei, the adjacent brainstem and the cerebellum. The intrinsic firing properties of vestibular ganglion cells (VGCs) are heterogeneous and have been classified into phasic, intermediate and tonic firing types on the basis of their response to injected depolarizing currents. A previous study from our group showed that the proportion of phasic discharging VGCs decreased during the first postnatal weeks. Moreover, α-dendrotoxin (α-DTX), a Kv1 potassium channels antagonist, turned neuron phasic firing to tonic, thus suggesting that these channels play an important role in the developmental changes of VGCs firing patterns. Here, by using immunohistochemistry, Western blotting and quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR), we explored the change in the expression of α-DTX-sensitive K(+) channels, Kv1.1, Kv1.2 and Kv1.6 in rat VGCs during early postnatal periods. We showed that expression of Kv1.6 protein is down-regulated together with expression of Kv1.6 mRNA after postnatal day 7 in rat VGCs whereas expression of Kv1.1 and Kv1.2 proteins did not change during the same developmental period. Our results suggest that down-regulation of the Kv1.6 protein and mRNA may be associated with maturation of excitable properties of primary vestibular neurons.

Clinical characteristics of inferior vestibular neuritis.

CONCLUSIONS: Inferior vestibular neuritis (IVN) is a relatively minor subtype of vestibular neuritis (VN) and its clinical characteristics are unique. OBJECTIVES: To clarify clinical characteristics of IVN in comparison with conventional VN. METHODS: This was a retrospective case series review. Caloric responses and cervical vestibular evoked myogenic potential (cVEMP) responses were measured in 71 patients with VN. The patients were classified into three groups: (1) IVN group, who showed only asymmetrical cVEMP responses; (2) superior VN (SVN) group, who showed only asymmetrical caloric responses; (3) total VN (TVN) group, who showed asymmetrical responses in both tests. The clinical records of time course of subjective symptoms (duration of attack, duration of hospitalization, and time to remission) were reviewed and other profiles (age, sex, affected side, acute symptoms, and sequelae) were evaluated. RESULTS: Of the 71 patients with VN, 13 (18%) were classified as having IVN. The mean age and time to remission of patients with IVN (44.2 ± 4.8 years, 0.9 ± 0.5 months) were significantly lower and shorter, respectively, than those of patients with TVN (57.3 ± 2.5 years, 4.9 ± 4.7 months). There were no significant differences in other symptoms and profiles among the three groups. No patients with IVN showed benign paroxysmal positional vertigo as a sequela.

Elucidation of the therapeutic enhancer mechanism of poly-S-nitrosated human serum albumin against multidrug-resistant tumor in animal models.

Human serum albumin (HSA) is the most abundant circulating protein and its S-nitrosated form serves as a reservoir of nitric oxide (NO). Previously, we prepared poly-S-nitrosated HSA (Poly-SNO-HSA) by incubation with Traut's Reagent and isopentyl nitrite and evaluated its potential as a novel anticancer agent through apoptosis involving the caspase-3 pathway. Recently, NO donors such as nitroglycerin were reported to revert the resistance to anticancer agents. Therefore, now we have evaluated the effect of the above type of Poly-SNO-HSA on the resistance to doxorubicin (dx) in human myelogenous leukemic cells (K562 cells). P-gp expression and dx accumulation in K562 and dx-resistant K562 cells (K562/dx cells) were quantified using Western blot and FACS analysis, respectively. Compared with parent K562 cells, higher expression of P-gp and lower accumulation of dx were shown in K562/dx cells. Poly-SNO-HSA caused increased dx accumulation in K562/dx cells by decreasing the expressions of P-gp and HIF-1α. Other experiments with the guanylate cyclase inhibitor ODQ and 8-Br-cGMP revealed that also a cGMP signaling pathway is involved in the Poly-SNO-HSA induced increase in dx accumulation. Furthermore, in vivo studies showed that co-treatment with Poly-SNO-HSA enhanced the anticancer effect of dx in K562/dx cells-bearing mice. Thus, in addition to its proapoptotic effect Poly-SNO-HSA can in an efficient manner revert drug resistance both in vitro and in vivo, and two pathways for this effect have been identified.

Differential diagnosis of proptosis: report of 2 cases.

We rarely encounter patients with proptosis, however, it is known that inflammation and extension of paranasal sinus tumors may cause this condition. We should consider the diseases that may cause proptosis to facilitate the diagnosis. Recently, we treated proptosis in 2 cases, one with inflammatory myofibroblastic tumor (IMT) and the other with malignant lymphoma. As these 2 diseases show various clinical features and these features frequently overlap, it is difficult to differentiate between IMT and malignant lymphoma without pathological examinations. In this study, we review the relevant literature reports and discuss the difficulties in establishing a clinicopathological diagnosis and present a slight distinction in magnetic resonance imaging.

Vocal cord abductor paralysis in multiple system atrophy: a case report.

Multiple system atrophy (MSA) is a progressive neurodegenerative disease that is characterized by varying degrees of parkinsonism and cerebellar, corticospinal, and autonomic dysfunction. Vocal cord abductor paralysis (VCAP) is considered a sign of a poor prognosis in MSA, because it is a life-threatening complication that may cause nocturnal sudden death. This case report presents a patient who was treated for Parkinson's disease, and complained of dizziness and sleep apnea. We examined VCAP using fiberoptic laryngoscopy as the possible cause of sleep apnea. VCAP usually occurs in the advanced stages of MSA and is accompanied by a worsening of other symptoms. Optokinetic nystagmus was severely impaired and the caloric test response was bilaterally absent. Objective findings such as VCAP and abnormal neuro-otological results led to the diagnosis of MSA.