Higher Cardio-Ankle Vascular Index Values in Patients With Vestibular Neuritis May Indicate a Better Prognosis.

BACKGROUND: The presumed etiology of vestibular neuritis (VN), a sudden onset of spontaneous vertigo without auditory or cranial nerve symptoms, includes viral infections and vascular disorders. However, no clinical test for estimating vascular disorders in VN has been reported. Moreover, estimating the etiology of VN is important to predict the prognosis and select appropriate treatment. This study aimed to evaluate the cardio-ankle vascular index (CAVI), which reflects arterial stiffness and elasticity, as an additional indicator for estimating the prognosis and etiology of VN. MATERIALS AND METHODS: Among 207 consecutive patients with suspected VN, 88 patients diagnosed with definite VN were enrolled. Age, initial and final percent canal paresis (CP) in the caloric test, CAVI, presence or absence of vestibular-evoked myogenic potential asymmetry, and medical history were evaluated using univariate and multivariate analyses. RESULTS: Patients with VN with high CAVI had a better prognosis than those with low CAVI. High CAVI was a factor for improvement in percent CP, in addition to younger age and less severe initial percent CP in the Cox proportional hazard model. CONCLUSION: CAVI can be an additional indicator for estimating the prognosis and etiology of VN. This indicator can potentially be applied to other diseases, including vascular disorders with other etiologies.

High Cardio-Ankle Vascular Index Values in Idiopathic Sudden Sensorineural Hearing Loss Patients Indicate Better Prognosis.

OBJECTIVE: Vascular disorders and viral infections are the presumed etiologies of idiopathic sudden sensorineural hearing loss (ISSNHL) and acute sensorineural hearing loss, with no identifiable cause. However, no clinical test for estimating the extent of vascular involvement in ISSNHL has been reported despite its potential impact on prognosis and treatment. We investigated the correlation between the cardio-ankle vascular index (CAVI), which reflects arterial stiffness and elasticity, and hearing improvement to ascertain its usefulness as an additional indicator of ISSNHL prognosis and etiology. METHODS: We enrolled 182 patients diagnosed with definite ISSNHL. The percentage of mild ISSNHL patients and that of patients experiencing no change were compared between the high-CAVI and low-CAVI groups. Age, initial and final pure-tone average (PTA) values, CAVI, presence or absence of vertigo, and medical histories were retrospectively reviewed and included in univariate and multivariate analyses. RESULTS: The percentage of mild ISSNHL patients was smaller in the high-CAVI group than in the low-CAVI group, whereas the percentage of patients experiencing no change was smaller in the high-CAVI group than in the low-CAVI group, although patients in the high-CAVI group were significantly older than those in the low-CAVI group. The Cox proportional hazard model revealed that high CAVI, hypertension, younger age, and initial PTA <90 dB were associated with hearing improvement. CONCLUSIONS: ISSNHL in patients with high CAVI was more severe but had a better prognosis than that in those with low CAVI. CAVI may help evaluate diseases of vascular and other etiologies, as well as ISSNHL.

Efficacy and safety of Infliximab for steroid-resistant immune-related adverse events: A retrospective study.

The present study investigated outcomes of infliximab (IFX) treatment among 8 Japanese patients with various types of cancer (4 with malignant melanoma, 3 with lung cancer and 1 with renal cancer) who developed severe steroid-resistant immune-related adverse events (irAEs) in association with immune checkpoint inhibitors (ICIs) to determine its efficacy and safety. Information, including patient background, treatment progress, examination data and imaging data, was collected retrospectively from electronic medical records. Adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Specific ICIs used were anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibody preparations in 7, 2 and 5 patients, respectively. Specific irAEs included grade 3 diarrhea/colitis in 7 patients and disseminated intravascular coagulation and myocarditis attributed to autoimmune activation in 1 patient. The median duration between systemic steroid and IFX treatments was 9 (range, 2-39) days. A total of 3 patients responded to IFX, 1 of whom responded after one dose and 2 responded after two doses. Respective diseases improved to grade 0 after a median of 18 (range, 9-32) days. No AEs were attributable to IFX. Additionally, anti-cytomegalovirus (CMV) and antibacterial agents were administered in parallel given the presence of CMV and Clostridium difficile (CD) infections in all patients, except in 1 exhibiting a marked IFX response after one dose. The combination of highly immunosuppressive IFX and high-dose systemic steroid administration over a long period presumably predisposed the patients to opportunistic enteric infections. Accordingly, early initiation of IFX treatment in conjunction with systemic steroid therapy should be considered for severe diarrhea/colitis and other irAEs. However, the possibility for CMV and CD infections should be recognized, and for these the treatment strategy may need to be modified at an early stage.

Japanese standard for clinical stabilometry assessment: Current status and future directions.

Stabilometry is a useful tool for examining patients with functional disorders of the vestibular system. However, measurement techniques and devices vary by country. Therefore, international standardization of stabilometry is mandatory to validate the exchange of important findings. This was advocated at the 1983 Posturography Meeting in Kyoto but has not been adopted worldwide, and each country has continued to use unique regional measurement methods. In Japan, stabilometry has widespread application in medical practice in conjunction with research into its applications. With a goal of international standardization, we present details of stabilometry measurement methods and their application in Japan, together with a brief history and potential future directions of stabilometry.

Dominant foot could affect the postural control in vestibular neuritis perceived by dynamic body balance.

During attacks of vestibular neuritis (VN), patients typically lose postural balance, with resultant postural inclination, gait deviation toward the lesion side, and tendency to fall. In this study, we examined and analyzed static and dynamic postural control during attacks of VN to characterize differences in postural control between right and left VN. Subjects were patients diagnosed with VN at the Department of Otolaryngology, Toho University Sakura Medical Center, and underwent in-patient treatment. Twenty-five patients who had spontaneous nystagmus were assessed within 3days after the onset; all were right-foot dominant. Right VN was detected in nine patients (men: 4, women: 5; mean age: 57.6±17.08years [range: 23-82]) and left VN in 16 patients (men: 10, women: 6; mean age: 58.4±14.08years [range: 23-85 years]); the percentages of canal paresis of right and left VN were 86.88±18.1% and 86.02±15.0%, respectively. Statistical comparisons were conducted using the independent t-test. In stabilometry, with eyes opened, no significant differences were found between patients with right and left VN. However, with eyes closed, the center of horizontal movement significantly shifted ipsilateral (p<0.01). The differences in the lateral and anteroposterior body tracking test (BTT) were statistically significant (p=0.0039 and p=0.0376, respectively), with greater changes in cases with right VN. Thus, the dominant foot might contribute to the postural control mechanism.

Clinical Efficiencies of Stabilometry and Visual Feedback Test for Differentiating the Patients with Psychogenic Vertigo from Healthy Subjects.

The psychogenic vertigo has been diagnosed based on subjective dizzy symptom without abnormal findings of oculomotor tests and vestibular tests. We investigated the characteristics of the postural control system in patients with psychogenic vertigo using stabilometry and Body Tracking Tests with a visual feedback test to assess the dynamic body balance. This study consisted of 14 patients with psychogenic vertigo and 92 aged-match healthy subjects. They were instructed to keep the center of pressure constantly in the target circle displayed on the screen in front of the subjects. The dynamic body balance was evaluated by the proportion of the center of pressure (COP) including in the target circle during the test. The psychogenic vertigo group showed a larger area and a smaller locus length per unit area in comparison with the healthy subject group (p<0.01). In spectral analysis with the maximum entropy method (MEM), the power of the medio-lateral and antero-posterior positional power spectrum under eyes open condition were significantly largest at around 0.125 Hz in the psychogenic vertigo group. No significant difference in the result of Body Tracking Tests with a visual feedback test was found between both groups. Our results suggest that the patients with psychogenic vertigo maintain body balance with extremely slowly and large movements for quiet stance during eyes open condition. The results of Body Tracking Tests with a visual feedback test may indicate that the spontaneous postural control itself in patients with psychogenic vertigo does not differ from that in healthy individuals. We believe that this test could be useful as one of the significant diagnostic tests for psychogenic vertigo.

Imaging of Triglycerides in Human Coronary Plaques by Color Fluorescent Angioscopy and Microscopy.

Native triglycerides (TG) deposited in the human vascular wall is not measurable or visible in vivo to date. We discovered that by exciting fluorescence at 345 nm and emitting at 420 nm, 3-amino-4-hydroxy-5-nitrobenzene sulfonic acid monohydrate (3-ANA) elicits a brown fluorescence that is characteristic of just TG. Therefore, localization of TG in coronary plaques and normal segments that were obtained from 19 human autopsy cases was examined by color fluorescent angioscopy (CFA) and microscopy using 3-ANA as a biomarker of TG. By CFA, the percentage (%) incidence of TG in 23 normal segments, 13 white plaques without lipid deposition, 18 white plaques (growth stage) with lipid deposition, 11 yellow plaques without necrotic core (mature stage), and 12 yellow plaques with necrotic core (advanced mature stage) was 95, 92, 50, 27, and 25, respectively. By color fluorescent microscopy, TG deposited mostly in the fibrotic area of the plaques. Contrary to the general belief that TG amount increases with plaque maturation, the results indicated that TG was deposited in most of the normal coronary segments, but the amount decreased with plaque maturation. If 3-ANA becomes applicable clinically, the CFA system could be used for imaging TG within coronary plaques in patients in vivo.

Molecular Imaging of Native Low-Density Lipoprotein by Near-Infrared Fluorescent Angioscopy in Human Coronary Plaques.

Low-density lipoprotein (LDL) is an important risk factor for coronary artery disease, but its localization within the human coronary arterial wall is poorly understood. Imaging of LDL in 30 coronary arteries excised from 15 subjects who underwent autopsy was performed using near-infrared fluorescent angioscopy system and using indocyanine green dye as a biomarker of LDL. The percentage incidence of LDL in 28 normal segments, 24 white plaques (early stage of plaque growth), and 21 yellow plaques (mature stage of plaque) classified by conventional angioscopy, was 14.2, 79.1 (p <0.01 vs normal segments and p <0.05 vs yellow plaques), and 28.5, respectively. Coronary near-infrared fluorescent angioscopy showed similar results in 7 patients in vivo. Our results suggested that LDL begins to deposit in the human coronary arterial wall in the early stage of atherosclerosis, increasingly deposits with plaque growth and decreases in the mature stage; and therefore, molecular therapy targeting LDL should be started before plaque maturation.

Subfraction analysis of circulating lipoproteins in a patient with Tangier disease due to a novel ABCA1 mutation.

Tangier disease, characterized by low or absent high-density lipoprotein (HDL), is a rare hereditary lipid storage disorder associated with frequent, but not obligatory, severe premature atherosclerosis due to disturbed reverse cholesterol transport from tissues. The reasons for the heterogeneity in atherogenicity in certain dyslipidemias have not been fully elucidated. Here, using high-performance liquid chromatography with a gel filtration column (HPLC-GFC), we have studied the lipoprotein profile of a 17-year old male patient with Tangier disease who to date has not developed manifest coronary atherosclerosis. The patient was shown to be homozygous for a novel mutation (Leu1097Pro) in the central cytoplasmic region of ATP-binding cassette transporter A1 (ABCA1). Serum total and HDL-cholesterol levels were 59mg/dl and 2mg/dl, respectively. Lipoprotein electrophoretic analyses on agarose and polyacrylamide gels showed the presence of massively abnormal lipoproteins. Further analysis by HPLC-GFC identified significant amounts of lipoproteins in low-density lipoprotein (LDL) subfractions. The lipoprotein particles found in the peak subfraction were smaller than normal LDL, were rich in triglycerides, but poor in cholesterol and phospholipids. These findings in an adolescent Tangier patient suggest that patients in whom these triglyceride-rich, cholesterol- and phospholipid-poor LDL-type particles accumulate over time, would experience an increased propensity for developing atherosclerosis.

The dominant foot affects the postural control mechanism: examination by body tracking test.

CONCLUSION: The antero-posterior (AP) body tracking test (BTT) showed that the dominant foot could affect the tilt angle of the sway movement, delineated by primary component analysis. Differences associated with the dominant foot could represent the difference in space perception of each person. OBJECTIVES: To examine whether the dominant foot could affect the postural control mechanism using the BTT. METHODS: Ninety-seven healthy participants enrolled in the study were classified into right-foot and left-foot dominance groups, and their performances were compared. For the BTT, each participant stood on a stabilometer and caught the movement of a visual target moving vertically (anterior-posterior) or horizontally by the center of pressure movement, displayed on a 14-inch screen monitor at 100 cm in front of the subject. The mean displacement angle of the obtained stabilogram was evaluated by principal component analysis. RESULTS: The AP BTT in the right-foot dominance group showed a clockwise tilt with a mean displacement angle of 3.022 ± 3.761°, whereas the group with left-foot dominance had a modest counter-clockwise tilt with a mean displacement angle of -0.694 ± 4.497°. This difference was found to be significant by the independent t test (p < 0.0001). In the lateral BTT, the mean displacement angles were not significant.

[Tracking axis of the body tracking test(BTT)].

We report herein on the use of the body tracking test (BTT), which is a method for quantitatively evaluating dynamic body balancing function, and how the body center moves during tracking by healthy subjects. We investigated 779 healthy subjects with no history of vertigo or balance disorder and a mean age of 37.9 years. Breakdown is as follows. Under 10 years old is 81 (37 boy and 44 girl), 10 years of age is 162 (73 boy and 89 girl), 20 years of age is 110 (43 men and 67 women), 30 years of age is 73 (44 male, 29 female), 40 years of age is 79 (49 men and 30 women), 50 years of age is 77 (40 men and 37 women), 60 years of age is 100 (53 men and 47 women), 70 years of age is 73 (27 men and 46 women), 80 years of age is 24 (15 men and 9 women). For the visual stimulus, we used a constant-speed antero-posterior (A-P) stimulus BTT and a constant-speed lateral BTT. BTT analysis involved principal axis analysis, in which the principal axis was the first principal component according to a principal component analysis technique. The axis tilt in the principal axis direction was assessed by calculating the coordinate Y-axis and X-axis tilt. In the anteroposterior (A-P) BTT, subjects of all ages exhibited an angle of tilt in the clockwise direction (the "plus" direction), together with the position vector and velocity vector. In the lateral BTT, we observed that the subjects tracked with a tilt in the counter-clockwise direction (the "minus" direction), together with the position vector and velocity vector. In terms of the subjects' ages, the angle of tilt from 0 degree in the antero-posterior (A-P) BTT showed the clockwise direction (the "plus" direction). In the lateral BTT, subjects 10 to 30 years of age exhibited tracking along the X-axis, with no observable tilt. Movement of the center of gravity may be a major acquired ability (practice) with respect to the direction of tilt of the tracking axis. Spatial sensory ability primarily involves the right parietal lobe of the brain, and somatosensory information from the left side of the body is believed to be used more for the positional relationships between the legs and the torso. Deviation of the principal axis appears to be related to the relationship between the dominant foot and the pivot foot, as well as to the functions of the parietal lobe that are involved in spatial sensing.

[Clinical evaluation of vertigo in menopausal women].

Vertigo is one of the usual menopausal symptoms. We have often examined some women under the complaint of vertigo related with the menopause. We diagnosed each disease based on neuro-otological examinations and investigated the characteristics of menopausal-associated vertigo. We studied 413 women aged 40-59 years old who complained of vertigo. There were 73 women with menopause symptoms (14 women introduced from the gynecologist in our medical center, 18 women had undergone treatment at another female clinic, and 41 women visited an otorhinolaryngologist first) compared with 340 women without menopause symptoms. In the menopause group, 41 (56.2%) cases were diagnosed as having benign paroxysmal positional vertigo (BPPV), 13 (17.8%) cases had Meniere's disease, sudden deafness with vertigo accounted 2 cases, one was an acoustic tumor, and so on. The percentage of patients with BPPV was almost same ratio between the menopause group (56.2%) and the non-menopause group (52.9%). The percentage of patients with Meniere's disease was higher markedly in the menopausal group (17.8%). than the non-menopause group (9.7%). Menopausal symptoms are caused not only by hot flashes related to a lack of estrogen but also by psychological factors. The onset of Meniere's disease can also be influenced by psychological factors. As for the diagnosis of Meniere's disease, we supposed the reason for the higher percentage in the menopausal group was its relationship with psychological factors. We could diagnose and treat some menopausal women with vertigo. We believe that joint consultation with a gynecologist and otorhinolaryngologist would be necessary to ensure an optimum quality of life for such patients.

Lateral medullary infarction presenting as isolated vertigo and unilateral loss of visual suppression.

Isolated vertigo is rare in lateral medullary infarction. We described early diagnostic challenges in such cases by a neuro-otological approach. We report a 56-year-old man who developed a lateral medullary infarction that presented as isolated vertigo. Before the day 4 from disease onset when diffusion-weighted magnetic resonance imaging (MRI) became positive, this patient showed unilateral loss of visual suppression, a central type of vestibular dysfunction. Since MRI abnormalities may not appear in the early few days from disease onset, unilateral loss of visual suppression might become an important diagnostic option for isolated vertigo due to a lateral medullary infarction. This finding is presumably relevant to the inferior olive lesion.

Visual Suppression is Impaired in Spinocerebellar Ataxia Type 6 but Preserved in Benign Paroxysmal Positional Vertigo.

Positional vertigo is a common neurologic emergency and mostly the etiology is peripheral. However, central diseases may mimic peripheral positional vertigo at their initial presentation. We here describe the results of a visual suppression test in six patients with spinocerebellar ataxia type 6 (SCA6), a central positional vertigo, and nine patients with benign paroxysmal positional vertigo (BPPV), the major peripheral positional vertigo. As a result, the visual suppression value of both diseases differed significantly; e.g., 22.5% in SCA6 and 64.3% in BPPV (p < 0.001). There was a positive correlation between the visual suppression value and disease duration, cerebellar atrophy, and CAG repeat length of SCA6 but they were not statistically significant. In conclusion, the present study showed for the first time that visual suppression is impaired in SCA6, a central positional vertigo, but preserved in BPPV, the major peripheral positional vertigo, by directly comparing both groups. The abnormality in the SCA6 group presumably reflects dysfunction in the central visual fixation pathway at the cerebellar flocculus and nodulus. This simple test might aid differential diagnosis of peripheral and central positional vertigo at the earlier stage of disease.

VGCC antibody-positive paraneoplastic cerebellar degeneration presenting with positioning vertigo.

A 70-year-old woman developed paraneoplastic cerebellar degeneration (PCD) due to P/Q-type and N-type voltage-gated calcium channel antibodies and small cell lung cancer, the main clinical manifestations of which were severe positioning vertigo and vomiting. Loss of the visual suppression of caloric nystagmus, spontaneous downbeat nystagmus, periodic alternating nystagmus, and positioning vertigo in our patient most probably corresponds to the cerebellar flocculus/paraflocculus lesion caused by PCD.

[Non-specific exercise therapy for benign paroxysmal postural vertigo].

We treated 1145 patients diagnosed as having benign paroxysmal postural vertigo at the Toho University Medical Center Sakura Hospital from August 2007 to July 2009 by the exercise therapy developed by us. The most advantageous characteristic of our method is that patients can perform the exercises themselves at their own pace in their homes, even if the affected side cannot be identified and/or the patients have any orthopedic cervical and/or spinal problems. In 80.7% and 91.7% of the patients in our case series, the vertigo was no longer present at one and three months, respectively. In addition, the vertigo disappeared within two weeks in the patients who were examined within one week of the start of the symptom. The longer the period between the onset of vertigo and the hospital visit, the longer the period needed for control of the symptom.

[Examination of dynamic body balance using the body tracking test in cases of vestibular neuronitis].

Body Tracking Test (BTT) is a testing method of the dynamic body balance function wherein movement of the center of gravity in accordance with a moving visual target stimulus is examined to evaluate the tracking function of the body. The objects were the patients who were diagnosed as having vestibular neuronitis at the Department of Otolaryngology in Toho University medical center Sakura hospital, and were undergoing hospital treatment. Lateral BTT was performed in 31 subjects, and antero-posterior (A-P) BTT in 45 subjects. Although gaze nystagmus was noted, inspection was enforced when a standing position posture was possible. In lateral BTT, the average (cm/second) horizontal direction body sway speed was compared, however, no clear lateral difference was noted. In the antero-posterior (A-P) BTT, it inquired using the direction body sway average center displacement (cm) of X. Deviation was seen by the affected side in stabilometry. Deviation was seen by the unaffected side in the antero-posterior (A-P) BTT. This phenomenon differs from the deviation pattern until now and is considered to involve participation of the higher centers.

[3D-CT highly useful in diagnosing foreign bodies in the paraesophageal orifice].

Multislice computed tomography (CT) enables rapid, easy construction of 3-dimensional CT images (3D-CT), aiding diagnostic imaging. 3D-CT is reported to be highly useful in diagnosing temporal bone disorders, in otorhinolaryngology, especially abnormal shape and the ossicular chain of the auditory ossicles and facial bone fractures. Given the complexity of laryngeal anatomy, 3D-CT is useful in diagnosing the extent of infiltration of laryngeal cancer and in examining vocal cord movement, which is difficult to evaluate by conventional CT, magnestic resonance imaging (MRI), and fiberscopy. Among patients seen for a suspected foreign body between June 2002 and May 2003, we chose 3 in whom laryngoscopy at the first examination could not detect a foreign body but in whom symptoms and findings suggested such presence in the paraesophageal orifice. In all 3 cases, 3D-CT imaging showed the size, length, location, and direction of the foreign body, providing information useful for the surgical approach.