Difference in Serum Levels of Vitamin D Between Canalolithiasis and Cupulolithiasis of the Horizontal Semicircular Canal in Benign Paroxysmal Positional Vertigo

BRIEF RESEARCH REPORT published: 01 March 2019 doi: 10.3389/fneur.2019.00176 Difference in Serum Levels of Vitamin D Between Canalolithiasis and Cupulolithiasis of the Horizontal Semicircular Canal in Benign Paroxysmal Positional Vertigo Takafumi Nakada 1*, Saiko Sugiura 1 , Yasue Uchida 1,2 , Hirokazu Suzuki 1 , Masaaki Teranishi 1,3 and Michihiko Sone 3 1 Department of Otorhinolaryngology, National Center for Geriatrics and Gerontology, Obu, Japan, 2 Department of Otorhinolaryngology, Aichi Medical University, Nagakute, Japan, 3 Department of Otorhinolaryngology, Nagoya University, Nagoya, Japan Edited by: Herman Kingma, Maastricht University, Netherlands Reviewed by: Nicolas Perez-Fernandez, Clínica Universidad de Navarra, Spain Michael C. Schubert, Johns Hopkins University, United States *Correspondence: Takafumi Nakada Specialty section: This article was submitted to Neuro-Otology, a section of the journal Frontiers in Neurology Received: 04 December 2018 Accepted: 11 February 2019 Published: 01 March 2019 Citation: Nakada T, Sugiura S, Uchida Y, Suzuki H, Teranishi M and Sone M (2019) Difference in Serum Levels of Vitamin D Between Canalolithiasis and Cupulolithiasis of the Horizontal Semicircular Canal in Benign Paroxysmal Positional Vertigo. Front. Neurol. 10:176. doi: 10.3389/fneur.2019.00176 Frontiers in Neurology | www.frontiersin.org Background and Purpose: In the horizontal canal benign paroxysmal positional vertigo (BPPV), cupulolithiasis shows apogeotropic direction changing nystagmus lasting more than 1 min, while canalolithiasis leads to geotropic direction changing nystagmus lasting < 1 min. The difference between cupulolithiasis and canalolithiasis is widely accepted to be the attachment of the displaced otoconia to the cupula of a semicircular canal. Several studies have shown a relationship between BPPV and vitamin D deficiency, but no studies have compared serum levels of vitamin D between canalolithiasis and cupulolithiasis patients. The purpose of this study was to clarify the difference in vitamin D serum level between canalolithiasis and cupulolithiasis of the horizontal canal. Methods: This retrospective study included 20 and 15 patients with canalolithiasis and cupulolithiasis of the horizontal canal, respectively. Serum levels of 25-hydroxyvitamin D [25(OH)D] during the acute phase of BPPV were measured. Results: The mean 25(OH)D serum level in patients with canalolithiasis and cupulolithiasis was 13.2 ± 1.4 and 20.4 ± 1.6 ng/mL, respectively, and the difference was statistically significant (p = 0.0014), also after adjusting for age and sex (p = 0.0351). Eighteen out of 20 (90%) and 5 of 15 (33%) patients were diagnosed with vitamin D deficiency in the canalolithiasis and cupulolithiasis groups, respectively, and this difference was also statistically significant (p = 0.0005). Conclusion: We found that serum vitamin D level in patients with canalolithiasis was significantly lower than that in patients with cupulolithiasis of the horizontal canal. Keywords: benign paroxysmal positional vertigo, vitamin D, canalolithiasis, geotropic, cupulolithiasis, apogeotropic 1 March 2019 | Volume 10 | Article 176 Nakada et al. Vitamin D in Canalolithiasis and Cupulolithiasis Statistical Analyses INTRODUCTION Statistical analysis was carried out with the Statistical Analysis System (SAS) package, version 9.3 (SAS Institute, Cary, NC, USA). The difference in the mean level of serum 25 hydroxyvitamin D between the groups was assessed using a general linear model to adjust for age and sex. A serum 25(OH)D level of <20 ng/mL was defined as vitamin D deficiency. The relationship between the diagnosis (canalolithiasis or cupulolithiasis) and vitamin D deficiency (< 20 ng/mL) was assessed using the chi squared test and logistic regression. The level of significance was set at p < 0.05. Benign paroxysmal positional vertigo (BPPV) is the most frequent vestibular disorder (1). It is caused by the abnormal stimulation of the cupula, upon changing head position, by otoconia, either floating or attached to the cupula, in any of the three semicircular canals. The Dix-Hallpike maneuver and the supine roll test are used to diagnose BPPV, and patients are treated through specific canalith-repositioning maneuvers, although remission can be expected within several days also without treatment (2). Among the semicircular canals, the posterior canal is the most affected for anatomical reasons. In the horizontal semicircular canal, canalolithiasis and cupulolithiasis exhibit the characteristic nystagmus: canalolithiasis leads to geotropic direction changing nystagmus lasting <1 min, while cupulolithiasis shows apogeotropic direction changing nystagmus lasting more than 1 min, in the supine roll test (3). In addition, when the otoconia fall into the short arm and directly onto the cupula, apogeotropic horizontal nystagmus are observed (short-arm canalolithiasis) (4). No nystagmus may be provoked in the contralateral spine position because the otoconia may fall out during the spine roll test in the contralateral direction. Moreover, rapid transition from apogeotropic to geotropic direction changing nystagmus during the supine roll test may be observed when otoconia are located in the anterior part of the horizontal canal (3). BPPV patients are at a high risk of fracture, associated with abnormal bone turnover (5). Vitamin D mainly controls the absorption of calcium and phosphate from the small intestine, which plays a crucial role in bone turnover (6). On the other hand, vitamin D deficiency can change the structure of the otoconia, which are made of calcium carbonate (7). Such structural changes may induce otoconia to easily detach from the otolith organ, leading to BPPV attacks. No studies have compared serum levels of vitamin D between canalolithiasis and cupulolithiasis patients, which we focused on. The purpose of this study was to clarify the difference in vitamin D serum level between canalolithiasis and cupulolithiasis of the horizontal canal. The results will contribute to explain the pathophysiological difference between canalolithiasis and cupulolithiasis. RESULTS A total of 38 patients were diagnosed with BPPV of the horizontal semicircular canal. Of these, 35 patients, followed up until the symptoms and nystagmus disappeared, were enrolled in the study, while 3 were excluded due to loss of follow up. Among the 35 participants, 20 were diagnosed with horizontal canal canalolithiasis (CAN), and 15 with horizontal canal cupulolithiasis (CUP). The age of the CAN group was 76.7 ± 7.1 years, with 17 females (85%), while that of the CUP group was 75.9 ± 5.4 years, with 6 females (40%). The difference in sex prevalence was statistically significant (p = 0.0055, Table 1A). The mean serum 25(OH)D level of in the CAN group was 13.2 ± 1.4 ng/mL [least square (LS) mean ± standard error (SE)] and that in the CUP group was 20.4 ± 1.6 ng/mL (LS means ± SE), a stati (...truncated)