ABSTRACT
PURPOSE: Patients often have basic audiometry (BA) but not objective diagnostic tests of the vestibular system (VNG) when complaining of symptoms of a vestibular disorder. The relationship of BA results to VNG results is unknown. This study sought to determine if BA scores are related to impaired VNG scores. MATERIALS AND METHODS: We reviewed electronic medical records at a tertiary care center, for patients seen between 2015 and 2021 who had had both a BA and a VNG (n = 651). BA subtests were pure tone averages, word recognition, and tympanogram. VNG subtests were cervical vestibular evoked myogenic potentials, Dix-Hallpike maneuvers, and bi-thermal caloric tests. All tests were summarized as normal/abnormal. RESULTS: More subjects had abnormal BA than abnormal VNG scores. Age but not sex was significantly related to abnormal scores. High BP was a significant comorbidity in 15 % of the sample, more in patients with abnormal than normal VNG scores. Although the abnormal BA and abnormal VNG were significantly related, pure tone averages and tympanogram scores were not related to VNG subtests. Abnormal word recognition with both ears combined was significantly related to normal and abnormal bi-thermal caloric tests. CONCLUSIONS: If the clinician needs to know of any VNG impairment, in general, then performing a BA without a VNG might suffice. If the clinician needs information about the details of possible vestibular impairment, then a VNG should be performed.
Subject(s)
Vestibular Diseases , Vestibular Evoked Myogenic Potentials , Vestibule, Labyrinth , Humans , Vertigo/diagnosis , Hearing , Vestibular Diseases/diagnosis , Caloric Tests , Vestibular Function TestsABSTRACT
Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine kinase, is highly expressed in the brain, but its function in the adult brain remains not well understood. In this study, we identify NLK as an interactor of huntingtin protein (HTT). We report that NLK levels are significantly decreased in HD human brain and HD models. Importantly, overexpression of NLK in the striatum attenuates brain atrophy, preserves striatal DARPP32 levels and reduces mutant HTT (mHTT) aggregation in HD mice. In contrast, genetic reduction of NLK exacerbates brain atrophy and loss of DARPP32 in HD mice. Moreover, we demonstrate that NLK lowers mHTT levels in a kinase activity-dependent manner, while having no significant effect on normal HTT protein levels in mouse striatal cells, human cells and HD mouse models. The NLK-mediated lowering of mHTT is associated with enhanced phosphorylation of mHTT. Phosphorylation defective mutation of serine at amino acid 120 (S120) abolishes the mHTT-lowering effect of NLK, suggesting that S120 phosphorylation is an important step in the NLK-mediated lowering of mHTT. A further mechanistic study suggests that NLK promotes mHTT ubiquitination and degradation via the proteasome pathway. Taken together, our results indicate a protective role of NLK in HD and reveal a new molecular target to reduce mHTT levels.
