Idiopathic benign paroxysmal positional vertigo with persistent vertigo/dizziness sensation is associated with latent canal paresis, endolymphatic hydrops, and osteoporosis.

OBJECTIVE: The aim of the present study was to examine the association of neuro-otological examination, blood test, and scoring questionnaire data with treatment-resistant intractability in idiopathic benign paroxysmal positional vertigo (BPPV) patients. METHODS: We experienced 1520 successive vertigo/dizziness patients at the Vertigo/Dizziness Center in Nara Medical University during May 2014 to April 2018. Six hundred and eleven patients were diagnosed as BPPV (611/1520; 40.2%) according to the diagnostic guideline of the International Classification of Vestibular Disorder in 2015. Among BPPV patients, there were 201 intractable patients (201/611; 32.9%), 66 of whom were idiopathic and enrolled to be hospitalized and receive neuro-otological examinations, including the caloric test (C-test), vestibular evoked cervical myogenic potentials (cVEMP), subjective visual vertical (SVV), glycerol test (G-test), electrocochleogram (ECoG), inner ear magnetic resonance imaging (ieMRI), blood tests including anti-diuretic hormone (ADH) and bone alkaline phosphatase (BAP), and self-rating questionnaires of depression score (SDS). Sixty-six patients were diagnosed as horizontal type cupula (hBPPVcu; n=30), horizontal type canal (hBPPVca; n=10), posterior type (n=20), and probable and/or atypical BPPV (n=6). Data are presented as ratios (+) of the number of idiopathic BPPV patients with examination and questionnaire data outside of the normal range. RESULTS: The ratio (+) data were as follows: C-test=21.2% (14/66), cVEMP=24.2% (16/66), SVV=48.5% (32/66), G-test=18.2% (12/66), ECoG=18.2% (12/66), ieMRI=12.1% (8/66), ADH=9.1% (6/66), BAP=13.6% (9/66), and SDS=37.9% (25/66). Multivariate regression analysis revealed that the periods of persistent vertigo/dizziness were significantly longer in BPPV patients with hBPPVcu, C-test (+), endolymphatic hydrops (+), and BAP (+) compared with those with negative findings. CONCLUSION: Although patients with idiopathic BPPV are usually treatable and curable within 1 month, the presence of hBPPVcu, canal paresis, endolymphatic hydrops, and elevated BAP may make the disease intractable, and thus require additional treatments.

Dehydration effects of a V2 antagonist on endolymphatic hydrops in guinea pigs.

We investigated the influence of vasopressin type 2 receptor antagonist (OPC-41061; Tolvaptan) on experimentally induced endolymphatic hydrops (EH) in guinea pigs. In the first series, the endolymphatic sac (ES) of the left ear of all animals was electrocauterized. Four weeks after surgery, the animals were allocated to four groups: three systemic applications groups (saline, OPC 10 and 100 mg/kg) and a local round window (RW) OPC 1 mg/body application group. We examined the histopathology of the temporal bones and assessed volumetric changes of the endolymphatic space in the cochlea and saccule. In the second series, we investigated the effects of systemic and topical applications of OPC on plasma vasopressin (p-VP) concentrations and plasma osmolality (p-OSM). In the first series, we found that EH was reduced in the OPC 10 mg/kg systemic and OPC RW application groups. In contrast, EH increased in the OPC 100 mg/kg systemic application group. In the second series, neither p-VP levels nor p-OSM were significantly different among the non-OPC, OPC 10 mg/kg systemic, and OPC RW application groups. However, in the OPC 100 mg/kg systemic application group, the p-VP level was significantly higher than that in other groups, and p-OSM was higher than that in the non-OPC group. The systemic application of a low dose of OPC and topical application of OPC resulted in reduced EH in the face of minimal systemic effects (p-VP and p-OSM). These findings suggest that OPC-41061 may be one useful treatment option for EH.

Diagnostic value of plasma antidiuretic hormone, electrocochleography, and glycerol test in patients with endolymphatic hydrops.

OBJECTIVE: To investigate the relationship between the plasma antidiuretic hormone (p-ADH) level, electrocochleogram (ECoG), and the glycerol test in patients with endolymphatic hydrops (ELH). PATIENTS AND METHODS: The subjects were 60 patients, including 51 with Ménière's disease (except for cochlear Ménière's disease), 7 with delayed ELH, and 2 with syphilitic ELH. The time period for measurements of the p-ADH level, ECoG and the glycerol test was within 4 weeks. RESULTS: 13 patients showed positive results for all tests. 58 patients showed positive results for at least one of three tests. Only 2 patients showed negative results for all tests. CONCLUSION: The p-ADH level, ECoG and the glycerol test show different selectivity of ELH detection. It is useful to perform all three tests to diagnose ELH.

Plasma antidiuretic hormone in cases with the early onset of profound unilateral deafness.

OBJECTIVE: The p-ADH level in cases of juvenile unilateral profound deafness (JUPD) and the timecourse of the level were examined to investigate whether or not an increase of p-ADH is involved in the development of delayed endolymphatic hydrops (DEH) in JUPD. MATERIALS AND METHODS: In 90 consecutive patients with unilateral profound or total sensorineural deafness with the onset in early childhood, pure-tone audiometric examination and the measurement of p-ADH and plasma osmolality (p-OSM) were followed up once or twice a year as far as possible. At every testing, we performed careful history-taking about episodic vertigo/dizziness, fluctuant hearing loss, and tinnitus in order to find out whether patients had experienced these clinical signs of the development of DEH. RESULTS: Means and standard deviation (S.D.) of p-ADH level and osmolality in all samples tested (n=368) were 7.3+/-7.0 pg/mL (0.7-52.0 pg/mL), and 288.6+/-4.4 mOsm/L (273-306 mOsm/L), respectively. The mean of p-ADH level was much higher than those previously reported in children and adolescents. High levels of p-ADH (over 5.0 pg/mL) were often observed in subjects between 6 and 19 years of age, but not so frequently in subjects of 20 years of age or older. Long-term follow-up of p-ADH levels revealed that DEH frequently developed in cases with persistent elevation of p-ADH. CONCLUSIONS: The elevation of p-ADH is likely to promote the development of DEH in cases of JUPD, although the underlying mechanism remains to be elucidated.

Antidiuretic hormone (ADH) and endolymphatic hydrops.

Plasma antidiuretic hormone (p-ADH) concentrations were determined with a radioimmunoassay, using a reversed-phase C18 silica column, in 300 patients with vertigo, dizziness and/or deafness; 119 of them had a diagnosis of Menière's disease. The p-ADH level was significantly elevated in patients with Meniere's disease and others with endolymphatic hydrops, e.g. cochlear Menière's disease or delayed hydrops. By contrast, the p-ADH level was not so high in cases without the endolymphatic hydrops. The increase in the p-ADH level was closely linked to vertigo attacks, the glycerol test results and an enhanced negative summating potential (-SP) in electrocochleogram (ECochG). These results lead to the assumption that disorders of ADH-dependent hormonal control in the inner ear may constitute the possible mechanism underlying vertiginous attacks and deafness in patients with endolymphatic hydrops.

The relationship between vasopressin and endolymphatic hydrops in the guinea pig.

Clinical studies have shown that plasma vasopressin level is significantly elevated in patients with Meniere's disease. Other reports indicated that histamine induced a very quick and high elevation of vasopressin level and caused nystagmus in experimentally produced endolymphatic hydrops. We became interested in further investigating the details of this relationship by studying the effect of experimental endolymphatic hydrops and histamine upon plasma vasopressin level in the guinea pig. The results are as follows: 1) Histamine increased the plasma vasopressin level in normal guinea pigs. 2) There was no statistically significant difference in the plasma vasopressin level between the hydrops model and normal guinea pigs. 3) Histamine increased the plasma vasopressin level more in the hydrops model group than in normals. 4) Plasma vasopressin level was elevated in the vertiginous model caused by inner ear anesthesia. Our results support those of clinical investigators who reported that the plasma vasopressin level was elevated more in the Meniere's disease group than any other equilibrium disorder group. It is possible that vasopressin is in someway involved in the development of endolymphatic hydrops.